DAC

WTSI CGP Data access committee

Dac ID Contact Person Email Access Information
EGAC00001000000 Data Sharing datasharing [at] sanger [dot] ac [dot] uk No additional information is available

This DAC controls 225 datasets:

Dataset ID Description Technology Samples
EGAD00001000100 Renal Matched Pair Cell Line Exome Sequencing Illumina Genome Analyzer II 10
EGAD00001000094 Cancer Genome Libraries Tests Illumina Genome Analyzer II 16
EGAD00001000128 Familial Thrombocytosis germline exome sequencing Illumina HiSeq 2000, Illumina HiSeq 2000; 4
EGAD00001000092 Cancer Exome Resequencing Illumina Genome Analyzer II 58
EGAD00001000104 Acute Lymphoblastic Leukemia Exome sequencing 2 Illumina Genome Analyzer II 97
EGAD00001000004 CLL cancer Sample Sequencing Illumina Genome Analyzer II, Illumina Genome Analyzer 5
EGAD00001000002 Massive genomic rearrangement acquired in a single catastrophic event during cancer development 11
EGAD00001000095 Acute Myeloid Leukemia Sequencing Illumina Genome Analyzer II 9
EGAD00001000081 Splenic Marginal Zone Lymphoma with villous lymphocytes exome sequencing Illumina HiSeq 2000 1
EGAD00001000089 Acute Lymphoblastic Leukemia Exome sequencing Illumina Genome Analyzer II 20
EGAD00001000070 TMD_AMLK Exome Study Illumina HiSeq 2000, Illumina HiSeq 2000; 50
EGAD00001000075 Gastric and Esophageal tumour rearrangement screen Illumina HiSeq 2000 32
EGAD00001000111 CML Discovery Project Illumina Genome Analyzer II 6
EGAD00000000055 COLO-829 is a publicly available immortal cancer cell line and COLO-829BL is a lymphoblastoid cell line derived from the same patient Illumina Genome Analyzer II 2
EGAD00001000072 Fanconi Anemia transformation to AML Illumina HiSeq 2000 6
EGAD00001000149 A Comprehensive Catalogue of Somatic Mutations from a Human Cancer Genome Illumina HiSeq 2000 2
EGAD00000000053 Sequencing data from Breast Cancer samples Illumina Genome Analyzer II 1
EGAD00000000054 NCI-H209 is an immortal cell line derived from a bone marrow metastasis of a patient with small cell lung cancer, taken before chemotherapy. The specimen showed histologically typical small cells with classic neuroendocrine features. NCI-BL209 is an EBV-transformed B-cell line derived from the same patient as the small cell lung cancer cell line, NCI-H209 Life Tech - Solid 1
EGAD00001001872 Targeted exome sequencing of patient derived xenografts from primary colorectal tumours and liver metastases. This dataset contains all the data available for this study on 2016-01-06. Illumina HiSeq 2000; 333
EGAD00001001873 AML emerges as a consequence of accumulating independent genetic aberrations that direct regulation and/or dysfunction of genes resulting in aberrant activation of signalling pathways, resistance to apoptosis and uncontrolled proliferation. Given the significant heterogeneity of AML genomes, AML patients demonstrate a highly variable response rate and poor median survival in response to current chemotherapy regimens. For the past 4 years we have conducted gene expression profiling on purified bone marrow populations equating to normal haematopoietic stem and progenitor cells from healthy subjects and patients with de novo AML in order to identify AML signatures of aberrantly expressed genes in cancer versus normal. We are now applying a series of bioinformatic methodologies combined with clinical and conventional diagnostic data to establish novel genomics strategies for improved prognostication of AML. Additionally, we use our AML signatures to unravel oncogenic signalling pathway activities in AML patients and test inhibitory drugs for these pathways inn preclinical therapeutic programmes. We consider that superimposing GEP and clinical data for our AML patient cohort with additional data on their mutational status will significantly improve the prognostic power of the study as well as unravel yet unknown mutations associated with aberrant signalling activities of oncogenic pathways. Illumina HiSeq 2000; 215
EGAD00001000444 Cancer is driven my mutations in the genome. We will uncover the mutations that give rise to Ewing's sarcoma, a bone tumour that largely affects children. We will use second generation Illumina massively parallel sequencing, and bespoke software, to characterise the genomes and transcriptomes of Ewing's sarcoma tumours. Illumina HiSeq 2000; 3
EGAD00001000098 FRCC Exome sequencing Illumina Genome Analyzer II 16
EGAD00001000175 Identification of SPEN as a novel cancer gene and FGFR2 as a potential therapeutic target in adenoid cystic carcinoma Illumina Genome Analyzer II; 48
EGAD00001000101 ADCC Exome Sequencing Illumina Genome Analyzer II, Illumina HiSeq 2000; 125
EGAD00001000127 Burden of Disease in Sarcoma Illumina HiSeq 2000, Illumina HiSeq 2000; 220
EGAD00001000226 Chordoma is a rare malignant bone tumor that expresses the transcription factor T. We conducted an association study of 40 patients with chordoma and 358 ancestry-matched, unaffected individuals with replication in an independent cohort. Whole-exome and Sanger sequencing of T exons reveals a strong risk association ( allelic odds ratio (OR) = 4.9, P = 3.3x10-11, CI= 2.9-8.1) with the common (minor allelic frequency >5%) non-synonymous SNP rs2305089 in chordoma, which is exceptional in cancer genetics. Illumina Genome Analyzer II;, Illumina HiSeq 2000; 18
EGAD00001000119 Chordoma Exome Sequencing Illumina HiSeq 2000, Illumina Genome Analyzer II, Illumina HiSeq 2000; 50
EGAD00001000145 Matched Pair Cancer Cell line Whole Genomes Illumina HiSeq 2000, Illumina HiSeq 2000; 58
EGAD00000000051 Sequencing data from matching Renal Carcinoma samples Illumina Genome Analyzer II 25
EGAD00001000001 Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma 18
EGAD00001000287 Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 25 renal cancers and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 50 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes. Illumina Genome Analyzer II; 54
EGAD00001000014 Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 25 renal cancers and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 50 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes. Illumina Genome Analyzer II;, Illumina Genome Analyzer II 54
EGAD00001000130 Breast Cancer Matched Pair Cell Line Whole Genomes Illumina HiSeq 2000, Illumina HiSeq 2000; 22
EGAD00001000144 Lung Cancer Whole Genomes Illumina HiSeq 2000, Illumina HiSeq 2000; 18
EGAD00001000090 Glioma cell lines rearrangement screen Illumina Genome Analyzer II 3
EGAD00001000069 Lung Rearrangement Study Illumina HiSeq 2000 48
EGAD00001000067 Cancer Single Cell Sequencing Illumina HiSeq 2000, Illumina HiSeq 2000; 16
EGAD00001000154 Single-cell genome sequencing reveals DNA-mutation per cell cycle Illumina HiSeq 2000, Illumina Genome Analyzer II 12
EGAD00001000125 Chondrosarcoma Exome Illumina HiSeq 2000, Illumina HiSeq 2000; 104
EGAD00010000452 Chondrosarcoma case sample genotype using Affymetrix SNP6.0 Affymetrix_SNP6 36
EGAD00001000093 Breast Cancer Exome Resequencing Illumina Genome Analyzer II 21
EGAD00001000080 Genomics of Colorectal Cancer Metastases - Massively Parallel Sequencing of Matched Primary and Metastatic tumours to Identify a Metastatic Signature of Somatic Mutations (MOSAIC) Illumina HiSeq 2000, Illumina HiSeq 2000; 351
EGAD00001000091 Non Tumour Renal Cell Line Sequencing Illumina Genome Analyzer II 1
EGAD00001000078 ALK inhibitors in the context of ALK-dependent cancer cell lines Illumina HiSeq 2000, Illumina HiSeq 2000; 16
EGAD00001000013 CLL Cancer Whole Genome Sequencing Illumina Genome Analyzer II 19
EGAD00001000077 CRLF2 sequencing project Exomes Illumina HiSeq 2000 26
EGAD00001000005 Various Cancer Fusion Gene Sequencing Illumina Genome Analyzer II;, Illumina Genome Analyzer II 14
EGAD00001000068 Multifocal Breast Project Illumina Genome Analyzer II, Illumina HiSeq 2000; 22
EGAD00001000142 Renal Follow Up Series Illumina HiSeq 2000, Illumina HiSeq 2000; 637
EGAD00001000339 Multiple myeloma is an incurable plasma cell malignancy whose molecular pathogenesis is incompletely understood. We used whole exome sequencing, copy number profiling and cytogenetic to analyses 84 samples from 67 patients with myeloma. In addition to known myeloma genes, we identify new candidate genes, including truncations of SP140, ROBO1 and FAT3 and clustered missense mutations in EGR1. We find oncogenic mutations in cancer genes not previously implicated in myeloma, including SF3B1, PI3KCA and PTEN. We define diverse processes contributing to the mutational repertoire, including kataegis and somatic hypermutation. Most cases have at least one cluster of subclonal variants, including subclonal driver mutations, implying on-going tumor evolution. Serial samples revealed diverse patterns of clonal evolution, including linear evolution, differential clonal response and branching evolution. Our findings reveal the myeloma genome to be heterogeneous across patients and, within individual patients, to exhibit diversity in clonal admixture and dynamics in response to therapy. Illumina Genome Analyzer II;, Illumina HiSeq 2000; 154
EGAD00001000074 Integrative Oncogenomics of Multiple Myeloma Illumina HiSeq 2000, Illumina Genome Analyzer II 174
EGAD00010000395 Myeloma case sample genotype using Affymetrix SNP6.0 Affymetrix_SNP6 19
EGAD00001001453 The project is to evaluate the genomic binding sites of the histone demethylase JARID1C. This gene was recently identified in CGP as a novel recessive cancer gene in human renal cell carcinoma. Illumina Genome Analyzer II; 4
EGAD00001000359 In this study we will sequence the transcriptome of Verified Cancer Cell lines. This will be married up to whole exome and whole genome sequencing data to establish a full catalog of the variations and mutations found. Illumina HiSeq 2000; 2
EGAD00001000124 Sequencing Acute Myeloid Leukaemia Illumina HiSeq 2000, Illumina HiSeq 2000; 4
EGAD00001000064 Cell Line Sub Clone Rearrangement Screen Illumina Genome Analyzer II 6
EGAD00001000097 Matched breast cancer fusion gene study Illumina Genome Analyzer II 46
EGAD00001000143 Xenograft Seqeuncing Illumina HiSeq 2000, Illumina HiSeq 2000; 16
EGAD00001000062 ADCC Rearrangement Screen Illumina HiSeq 2000, Illumina Genome Analyzer II 14
EGAD00001000066 Breast Cancer Follow Up Series Illumina Genome Analyzer II 288
EGAD00001000076 CRLF2 sequencing project Illumina HiSeq 2000 13
EGAD00001000121 Breast Cancer Whole Genome Sequencing Illumina HiSeq 2000 6
EGAD00001000007 Osteosarcoma Sequencing Illumina Genome Analyzer II;, Illumina Genome Analyzer II 43
EGAD00001000112 Identifying Novel Fusion Genes in Myeloma Illumina Genome Analyzer II 6
EGAD00001000079 PREDICT Illumina HiSeq 2000, Illumina HiSeq 2000; 186
EGAD00001000099 Meningioma Exome Illumina Genome Analyzer II 26
EGAD00001000065 Mixed Leukemia Rearrangement Screen Illumina Genome Analyzer II 5
EGAD00001000071 Kaposi sarcoma exome Illumina HiSeq 2000 20
EGAD00001000116 Acute Lymphoblastic Leukemia Sequencing Illumina HiSeq 2000, Illumina Genome Analyzer II, Illumina HiSeq 2000; 61
EGAD00000000052 Sequencing data from natching Pancreatic Carcinoma samples Illumina Genome Analyzer II 25
EGAD00001000082 20 Matched Pair Breast Cancer Genomes Illumina HiSeq 2000;ILLUMINA, Illumina Genome Analyzer II;ILLUMINA 42
EGAD00001000073 MDSMPN Rearrangement Screen Illumina HiSeq 2000, Illumina HiSeq 2000; 11
EGAD00001000248 RNAseq Pulldown Illumina HiSeq 2000; 6
EGAD00001000050 Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes Illumina Genome Analyzer II 13
EGAD00001000084 Matched Ovarian Cancer Sequencing Illumina Genome Analyzer II 23
EGAD00001000266 This Study uses a focused bespoke bait pull down library method to target findings of Osteosarcoma whole genome and whole exome sequencing studies in order to validate findings. This method will also be used on a larger set of tumour only samples in order to find precedence of these findings in a larger set of patient samples. Illumina HiSeq 2000; 110
EGAD00001000367 Genomic libraries (500 bps) will be generated from total genomic DNA derived from lung cancer patients and subjected to short paired end sequencing on the llumina platform. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions. Illumina HiSeq 2000; 5
EGAD00001000389 Cancer is driven by mutations in the genome. We will uncover the mutations that give rise to Ewing's sarcoma, a bone tumour that largely affects children. We will use second generation Illumina massively parallel sequencing, and bespoke software, to characterise the genomes and transcriptomes of Ewing's sarcoma tumours. Illumina HiSeq 2000; 20
EGAD00001000369 We propose to definitively characterise the somatic genetics of a number of pediatric malignant tumours including ependymoma, high grade glioma and central nervous system primitive neurectodermal tumours through generation of comprehensive catalogues of somatic mutations by high coverage genome sequencing. Illumina HiSeq 2000; 3
EGAD00001000273 This Study uses a focused bespoke bait pull down library method to target findings of Meningioma whole genome and whole exome sequencing studies in order to validate findings. This method will also be used on a larger set of tumour only samples in order to find precedence of these findings in a larger set of patient samples. Illumina HiSeq 2000; 147
EGAD00001000246 Integrative Oncogenomics of multiple myeloma Illumina HiSeq 2000; 106
EGAD00001000361 This is a small pilot data set to test the feasibility of cDNA exomes across 1200 cancer cell line panel. cDNA exomes or Fus-seq is further explained in this studies Abstract. Illumina HiSeq 2000; 3
EGAD00001000255 Testing the feasibility of genome scale sequencing in routinely collected FFPE cancer specimens versus matched fresh frozen samples Illumina HiSeq 2000; 32
EGAD00001000288 Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer accounting for 10-15% of cases. ILC differs from invasive ductal carcinoma (IDC)with respect to epidemiology, histology, and clinical presentation. Moreover, ILC is less sensitive to chemotherapy, more frequently bilateral, and more prone to form gastrointestinal, peritoneal, and ovarian metastases than IDCs. In contrast to IDC, the prognostic value of histological grade (HG) in ILC is controversial. One of the three major components of histological grading (tubule formation) is missing in ILC which hinders the process of grading in this histological subtype and results in the classification of approximately two thirds of ILC as HG 2. Over the last decade, a number of gene expression signatures have shed light onto breast cancer classification, allowing breast cancer care to become more personalized. With respect to the management of estrogen receptor (ER)-positive breast cancer, several gene expression signatures provide prognostic and/or predictive information beyond what is possible with current classical clinico-pathological parameters alone. Nevertheless, most studies using gene expression signature have not considered different histologic subtypes separately. Recently, a comprehensive research program has elucidated some of the biological underpinnings of invasive lobular carcinoma. Genetic material extracted from 200 ILC tumor samples were studied using gene expression profiling and identified ILC molecular subtypes. These proliferation-driven gene signatures of ILC appear to have prognostic significance. In particular, the Genomic Grade (GG) gene signature improved upon HG in ILC and added prognostic value to classic clinico-pathologic factors. In addition this study demonstrated that most ILC are molecularly characterized as luminal-A (~75%)followed by luminal-B (~20%) and HER2-positve tumors (~5%). Moreover, we investigated the prognostic value of known gene signatures/ gene modules in the same cohort of ILC. As a second step within the scope of this project, we aim to investigate the interactions between somatic ILC tumor mutations to observed transcriptome findings. To this end, we aim to perform somatic mutation analysis for the ILC tumors for which Affymetrix gene expression profiling is available. To this end, we will use a gene screen assay, which specifically interrogates the mutational status of a few hundreds of cancer genes. We believe that this pioneering effort will be fundamental for a tailored treatment of ILC with improvement in patients' outcome. Illumina HiSeq 2000; 1130
EGAD00001000354 Testing the feasibility of genome-scale sequencing in routinely collected formalin-fixed paraffin-embedded (FFPE) cancer specimens versus matched fresh-frozen samples using targeted pulldown capture prior to Illumina sequencing. Illumina HiSeq 2000; 81
EGAD00001000267 This Study uses a focused bespoke bait pull down library method to target findings of Chordoma whole genome and whole exome sequencing studies in order to validate findings. This method will also be used on a larger set of tumour only samples in order to find precedence of these findings in a larger set of patient samples. Illumina HiSeq 2000; 46
EGAD00001000289 Agilent whole exome hybridisation capture was performed on genomic DNA derived from cancer and matched normal DNA from the same patients. Next Generation sequencing performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes. Now we aim to re find and validate the findings of those exome libraries using bespoke pulldown methods and sequencing the products. Illumina HiSeq 2000; 12
EGAD00001000388 Genomic libraries (500 bps) will be generated from total genomic DNA derived from lung cancer patients and subjected to short paired end sequencing on the llumina platform. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions. Illumina HiSeq 2000; 15
EGAD00001000243 Melanoma-TIL Study Exomes Illumina HiSeq 2000; 43
EGAD00001000350 We propose to definitively characterise the somatic genetics of a number of pediatric malignant tumours including ependymoma, high grade glioma and central nervous system primitive neurectodermal tumours through generation of comprehensive catalogues of somatic mutations by high coverage genome sequencing. Illumina HiSeq 2000; 17
EGAD00001000252 Evaluation of PCR library method on whole genome samples Illumina HiSeq 2000; 12
EGAD00001000253 AML targeted resequencing study Illumina HiSeq 2000; 1972
EGAD00001000301 A couple of previously characterized and sequenced libraries will be repeated using a couple of differing size selection criteria and skim sequenced using an Illumina HiSeq. The resulting sequence will be analyzed to determine the optimal DNA library size for our specific downstream analysis. Illumina HiSeq 2000; 1
EGAD00001000392 Agilent whole exome hybridisation capture was performed on genomic DNA derived from Chondrosarcoma cancer and matched normal DNA from the same patients. Next Generation sequencing performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes. Now we aim to re find and validate the findings of those exome libraries using bespoke pulldown methods and sequencing the products. Illumina MiSeq; 60
EGAD00001000302 This experiment is looking at the mutational signatures generated by engineered HRAS mutations by using whole genome sequence generated on massively parallel next generation sequencers. Illumina HiSeq 2000; 6
EGAD00001000245 Pulldown cytosine deaminases Illumina HiSeq 2000; 20
EGAD00001000247 Integrative Oncogenomics of multiple myeloma Illumina HiSeq 2000; 51
EGAD00001000264 Resistance towards chemotherapy is one of the main causes of treatment failure and death among breast cancer patients.The main objective of this project is to identify genetic mechanisms causing some breast cancer patients not to respond to a particluar type of chemotherapy (epirubicin) while other patients respond very well to the same treatment. In the project we will perform genome / exome sequencing of a selection of breast cancer patients (n=30). These patients are drawn from a cohort where all patients have recieved treatment with epirubicin monotherapy before surgical removal of a locally advanced breast tumour, and where all patients have been subjected to objective evaluation of the response to the therapy. Subsequent to sequencing, we will analyse the data and compare with the clinical data for each patient (object response to therapy). The main aim being to identify mutations that are associated with resistance to epirubicin. Identification of mutations with strong predictive value, may have a direct impact on cancer treatment since it opens the possibility for genetic testing of a tumour, and desicion on which drug is likely to work best, prior to treatment start. Illumina HiSeq 2000; 29
EGAD00001000349 These samples are from locally advanced breast cancers that have been treated with epirubicin monotherapy before surgery. We will sequence some samples from patients with good response to the therapy and some with poor response to the therapy. Illumina HiSeq 2000; 33
EGAD00001000360 The genome-wide landscape of somatically acquired mutations in mesothelioma has not been deeply characterised to date, but advances in DNA sequencing technology now allow this to be addressed comprehensively. Harnessing massively parallel DNA sequencing platforms, we will identify somatically acquired point mutations in all coding regions of the genome from patients with mesothelioma. In addition, using paired-end sequencing, we will map copy number changes and genomic rearrangements from the same patients. Illumina HiSeq 2000; 232
EGAD00001000265 This Study uses a focused bespoke bait pull down library method to target findings of Chondrosarcoma whole genome and whole exome sequencing studies in order to validate findings. This method will also be used on a larger set of tumour only samples in order to find precedence of these findings in a larger set of patient samples. Illumina HiSeq 2000;ILLUMINA 190
EGAD00001000338 We propose to definitively characterise the somatic genetics of ER+ve, HER2-ve breast cancer through generation of comprehensive catalogues of somatic mutations in breast cancer cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses. Illumina HiSeq 2000; 3
EGAD00001000606 Background Massively parallel sequencing technology has transformed cancer genomics. It is now feasible, in a clinically relevant time-frame, for a clinically manageable cost, to screen DNA from patient tumours for mutations essentially genome-wide. The challenge for personalised medicine will be to increase the sample size to thousands or tens of thousands of well-characterised cases in order to attain sufficient statistical power to stratify patients accurately across the complexity and genomic heterogeneity expected for most of the common tumour types. Currently, whole genome sequencing on this scale is not feasible, and targeted sequencing of relevant portions of the genome will be required. Pilot data We have developed protocols for large-scale, multiplexed sequencing of 100-200 genes in thousands of samples. Essentially, using robotic technology, genomic DNA from the cancer specimen is processed into sequencing libraries with unique DNA barcodes, thereby allowing sequencing reads to be attributed to the sample they derive from. Currently, these sequencing libraries can be generated in a 96-well format using fully automated protocols, and we are exploring methods to expand this to a 384-well format. The sequencing libraries are pooled and hybridized to custom sets of RNA baits representing the genomic regions of interest. Sequencing of the pulled-down libraries is done in pools of 48-96 samples per lane of an Illumina Hi-Seq. This protocol is already implemented at the Sanger Institute. We have published proof that somatic mutations in novel cancer genes can be identified from exome-wide sequencing. In unpublished pilot data, we have established the feasibility of robotic library production, custom pull-down, and multiplexed sequencing of barcoded libraries for 100 known myeloid cancer genes across 760 myelodysplasia samples. Highlights of the data thus far analysed reveal that the coverage is remarkably even between samples; when 96 samples are run, average coverage per lane of sequencing is ~250, with 90-95% of targeted exons covered by >25 reads; known mutations can be discovered in the data set; and the protocol is amenable to whole genome amplified DNA. The bioinformatic algorithms for identification of substitutions and indels in pull-down data are well-established; we have pilot data proving that copy number changes, LOH and genomic rearrangements in specific regions of interest can also be identified by tiling of baits across the relevant loci. Proposal We propose to apply this methodology to 10000 samples from patients with AML enrolled in clinical trials over the last 10-20 years. Oncogenic point mutations and potentially genomic rearrangements will be identified, and linked to clinical outcome data, with a view to undertaking the following sorts of analyses: ? Identification of co-occurrence, mutual exclusivity and clusters of driver mutations. ? Correlation of prognosis with driver mutations and potentially gene-gene interactions ? Exploration of genomic markers of drug response Ultimately, we would like to be in a position to release the mutation data together with matched clinical outcome data to genuine medical researchers via a controlled access approach, possibly within the COSMIC framework (www.sanger.ac.uk/genetics/CGP/cosmic/). The vision here is to generate a portal whereby a clinician faced with an AML patient and his / her mutational profile can obtain a ?personalised? prediction of outcome, together with a fair assessment of the uncertainty of the estimate. With a sufficient sample size, there would also be the potential to develop decision support algorithms for therapeutic choices based on such data. Illumina MiSeq; 38
EGAD00001000638 Insertion of processed pseudogenes is known to occur in the germline but has not previously been observed in somatic cells. Formation of pseudogenes could represent a new class of mutation in cancers and a new source of potential driver events. Illumina HiSeq 2000; 20
EGAD00001000636 The ETV6-RUNX1 fusion gene, found in 25% of childhood acute lymphoblastic leukemia (ALL), is acquired in utero but requires additional somatic mutations for overt leukemia. We used exome and low-coverage whole-genome sequencing to characterize the critical secondary events associated with leukemic transformation. RAG-mediated deletions emerge as the dominant mutational process, accounting for at least 43% of genomic rearrangements and characterized by the presence of recombination signal sequence motifs near the breakpoints; incorporation of non-templated sequence at the junction and a ten-fold enrichment at promoters and enhancers of genes actively transcribed in early B-lineage development. Single-cell tracking shows that this mechanism is not restricted to one founder cell but is rather active throughout leukemic evolution. Integration of point mutation and rearrangement data identifies recurrent inactivation of ATF7IP and MGA as two new tumor suppressor genes.Thus, a remarkably parsimonious mutational process transforms ETV6-RUNX1 lymphoblasts, striking promoters and enhancers of the genes that normally control B-cell differentiation. Illumina Genome Analyzer II; 117
EGAD00001000634 The ETV6-RUNX1 fusion gene, found in 25% of childhood acute lymphoblastic leukemia (ALL), is acquired in utero but requires additional somatic mutations for overt leukemia. We used exome and low-coverage whole-genome sequencing to characterize the critical secondary events associated with leukemic transformation. RAG-mediated deletions emerge as the dominant mutational process, accounting for at least 43% of genomic rearrangements and characterized by the presence of recombination signal sequence motifs near the breakpoints; incorporation of non-templated sequence at the junction and a ten-fold enrichment at promoters and enhancers of genes actively transcribed in early B-lineage development. Single-cell tracking shows that this mechanism is not restricted to one founder cell but is rather active throughout leukemic evolution. Integration of point mutation and rearrangement data identifies recurrent inactivation of ATF7IP and MGA as two new tumor suppressor genes.Thus, a remarkably parsimonious mutational process transforms ETV6-RUNX1 lymphoblasts, striking promoters and enhancers of the genes that normally control B-cell differentiation. Illumina HiSeq 2000; 2
EGAD00001000635 The ETV6-RUNX1 fusion gene, found in 25% of childhood acute lymphoblastic leukemia (ALL), is acquired in utero but requires additional somatic mutations for overt leukemia. We used exome and low-coverage whole-genome sequencing to characterize the critical secondary events associated with leukemic transformation. RAG-mediated deletions emerge as the dominant mutational process, accounting for at least 43% of genomic rearrangements and characterized by the presence of recombination signal sequence motifs near the breakpoints; incorporation of non-templated sequence at the junction and a ten-fold enrichment at promoters and enhancers of genes actively transcribed in early B-lineage development. Single-cell tracking shows that this mechanism is not restricted to one founder cell but is rather active throughout leukemic evolution. Integration of point mutation and rearrangement data identifies recurrent inactivation of ATF7IP and MGA as two new tumor suppressor genes.Thus, a remarkably parsimonious mutational process transforms ETV6-RUNX1 lymphoblasts, striking promoters and enhancers of the genes that normally control B-cell differentiation. Illumina Genome Analyzer II;, Illumina HiSeq 2000; 50
EGAD00001000637 Insertion of processed pseudogenes is known to occur in the germline but has not previously been observed in somatic cells. Formation of pseudogenes could represent a new class of mutation in cancers and a new source of potential driver events. Illumina Genome Analyzer II;, Illumina HiSeq 2000; 4
EGAD00001000337 Illumina RNA-Seq will be performed on four Ewing's sarcoma cell lines and two control cell lines. RNA was extracted from all the lines using a basic Trizol extraction protocol. Illumina HiSeq 2000; 12
EGAD00001000658 Changes in gene dosage are a major driver of cancer1, engineered from a finite, but increasingly well annotated, repertoire of mutational mechanisms2-6. These processes operate over levels ranging from individual exons to whole chromosomes, often generating correlated copy number alterations across hundreds of linked genes. An example of the latter is the 2% of childhood acute lymphoblastic leukemia (ALL) characterized by recurrent intrachromosomal amplification of megabase regions of chromosome 21 (iAMP21)7,8 To dissect the interplay between mutational processes and selection on this scale, we used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. We find that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have ~2700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by chromothripsis involving both sister chromatids of the dicentric Robertsonian chromosome. In contrast, sporadic iAMP21 is typically initiated by breakage-fusion-bridge (BFB) events, often followed by chromothripsis or other rearrangements. In both sporadic and iAMP21 in rob(15;21)c individuals, the final stages of amplification frequently involve large-scale duplications of the abnormal chromosome. The end-product is a derivative chromosome 21 or a derivative originating from the rob(15;21)c chromosome, der(15;21), respectively, with gene dosage optimised for leukemic potential, showing constrained copy number levels over multiple linked genes. In summary, the constitutional translocation, rob(15;21)c, predisposes to leukemia through a novel mechanism, namely a propensity to undergo chromothripsis, likely related to its dicentric nature. More generally, our data illustrate that several cancer-specific mutational processes, applied sequentially, can co-ordinate to fashion copy number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes. Illumina Genome Analyzer II;, Illumina HiSeq 2000; 9
EGAD00001000324 We will sequence the RNA of lymphoblast samples, transformed with EBV, which have poikiloderma syndrome with mutations in c16orf57. The aim of the experiment is to characterise RNA structural effects in this disease. Illumina HiSeq 2000; 4
EGAD00010000488 Chondroblastoma case sample genotype using Affymetrix SNP6.0 Affymetrix_SNP6- 7
EGAD00001000663 This study aims to re-sequence findings from whole genome studies using a bespoke pulldown method to validate mutations in those genomes sequenced. Illumina HiSeq 2000; 47
EGAD00001000678 FFPE CPA accreditation of genome-scale sequencing in routinely collected formalin-fixed paraffin-embedded (FFPE) cancer specimens versus matched fresh-frozen samples using targeted pulldown capture prior to Illumina sequencing. Illumina HiSeq 2000; 341
EGAD00001000325 In this study, mutations present in a series of human melanomas (stage IV disease) will be determined, using autologous blood cells to obtain a reference genome. From each of the samples that are analyzed, tumour-infiltrating T lymphocytes have also been isolated. This offers a unique opportunity to determine which (fraction of) mutations in human cancer leads to epitopes that are recognized by T cells. The resulting information is likely to be of value to understand how T cell activating drugs exert their action. Illumina HiSeq 2000; 22
EGAD00001000630 In this study we will sequence the transcriptome of Verified Matched Pair Cancer Cell line tumour samples. This will be married up to whole exome and whole genome sequencing data to establish a full catalog of the variations and mutations found. Illumina HiSeq 2000; 7
EGAD00001000639 Insertion of processed pseudogenes is known to occur in the germline but has not previously been observed in somatic cells. Formation of pseudogenes could represent a new class of mutation in cancers and a new source of potential driver events. Illumina HiSeq 2000; 3
EGAD00001000899 We propose to definitively characterise the somatic genetics of Metastatic breast cancer through generation of comprehensive catalogues of somatic mutations in Metastatic breast cancer cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses. Illumina HiSeq 2000; 41
EGAD00001000652 Pulldown experiments will be performed on a number of patients with Myeloproliferative Neoplasms (MPN). The pulldown will be a bespoke design targeting known mutations, this pulldown will be sequenced and analysed to inform prevalence of mutations and to inform to the possibility of use as a diagnostic tool. Illumina HiSeq 2000; 1036
EGAD00001001050 We propose to biopsy 20 consented BRAF mutant melanoma patients at Addenbrooke's Hospital pre-treatment with vemurafenib and also upon the development of resistant disease, with the aim of using exome sequence and SNP6 data to identify novel sequence variants and copy number alterations that can be used to validate observed resistance mechanisms in our cell line models and also to use these models to inform as to likely candidate small molecule inhibitors to overcome resistance and that could be tested in the clinical trial setting. Illumina HiSeq 2000; 8
EGAD00001000707 Discovery of resistance mechanisms to the BRAF inhibitor vemurafenib in metastatic BRAF mutant melanoma by massively-parallel sequencing of tumour samples. Comparison of genomic characteristics of pretreatment 'sensitive' to recurrence 'resistant' tumours to identify the genetics of drug resistance. Illumina HiSeq 2000; 57
EGAD00001000624 Multifocality or multicentricity in breast cancer may be defined as the presence of two or more tumor foci within a single quadrant of the breast or within different quadrants of the same breast, respectively. This original classification of the breast cancer as multicentric or multifocal was based on the assumption that cancers arising in the same quadrant were more likely to arise from the same ductal structures than those occurring in separate areas of the breast. The problem with these definitions is that the ?quadrants? of the breast are arbitrary external designations, as no internal boundaries do exist. This project will therefore focus both on synchronous multifocal and multicentric tumors. The incidence of multifocal and multicentric breast cancers was reported to be between 13 and 75% depending on the definition used, the extent of the pathologic sampling of the breast and whether in situ disease is considered evidence of multicentricity (1). Although this incidence is variable, those figures show that it is a frequent phenomenon. Multiple (multifocal/multicentric) breast carcinomas, especially when occurring in the same breast, represent a real challenge for both pathologists and clinicians in terms of identifying the cellular origin and the best therapeutic management of the cancer. Multifocality or multicentricity has been associated with a number of more aggressive features including an increased rate of regional lymph node metastases and adverse patient outcome when compared with unifocal tumors (2-3), and a possible increased risk of local recurrence following breast conserving surgery (4). For the moment, the literature is divided on whether there is a corresponding impact on survival outcomes. Today, the current convention to stage and to treat multifocal and multicentric tumors is the classical tumor-node-metastasis (TNM) staging guidelines with which tumor size is assessed by the largest tumor focus without taking other foci of disease into consideration. If some papers, as the recent one from Lynch and colleagues, support the current staging convention (3), others, however, as Boyages et al. suggested that aggregate size and not the size of the largest lesion should be considered in order to refine the prognostic assessment of those tumors (5). On the top of that, the question whether multifocal/multicentric carcinomas are due to the spread of a single carcinoma throughout the breast or is due to multiple carcinomas arising simultaneously has been a matter of debate. Some studies suggested that multifocal breast cancer may result from either intramammary spread from a single primary tumor or multiple synchronous primary tumors; whereas others suggest that multiple breast carcinomas always arise from the same clone (6-8). Recently, Pietri and colleagues analyzed the biological characterization of a series of 113 multifocal/multicentric breast cancers (8) which were diagnosed over a 5-year period. The expression of estrogen (ER) and progesterone (PgR) receptors, Ki-67 proliferative index, expression of HER2 and tumor grading were prospectively determined in each tumor focus, and mismatches among foci were recorded. Mismatches in ER status were present in 5 (4.4%) cases and PgR in 18 (15.9%) cases. Mismatches in tumor grading were present in 21 cases (18.6%), proliferative index (Ki-67) in 17 (15%) cases and HER2 status in 11 (9.7%) cases. Interestingly, this heterogeneity among foci has led to 14 (12.4%) patients receiving different adjuvant treatments compared with what would have been indicated if we had only taken into account the biologic status of the primary tumor. This study therefore showed that differences in biological characteristics of multifocal/multicentric lesions play a crucial role in the adjuvant treatment decision making process. In this study, we will concentrate on a larger series of patients with multifocal invasive ductal breast cancer lesions. We aim at: 1. Evaluating the incidence of multifocality according to the different breast cancer molecular subtypes (ER-/HER2-, HER2+, ER+/HER2-). 2. Evaluating the incidence of multifocality in patients with hereditary breast cancer disease (presence of germline BRCA1 or BRCA2 mutations). Moreover, we would like to investigate if multifocal lesions with BRCA1 or BRCA2 mutations exhibit a characteristic combination of substitution mutation signatures and a distinctive profile of deletions as demonstrated recently by Nik-Zainal and colleagues (9). 3. Correlating multifocality with clinical information in order to define its influence on patients? survival (DFS and OS). 4. Carrying high coverage targeted gene sequencing of driver cancer genes and genes whose mutation is of therapeutic importance in order to compare clinically-relevant genetic differences between several multifocal breast cancer lesions. 5. Evaluating the impact of the distance between the different lesions on the clinical outcome but also on the genetic differences. 6. Comparing gene expression patterns between several multifocal breast cancer lesions and correlate them with the results of the targeted genes screen. 7. Characterizing the genomic and transcriptomic status of cancer related genes in metastatic lesions (local recurrence, positive lymph node or distant metastatic sites) from the same multifocal invasive ductal breast cancer patients in order to evaluate the consequence of genomic and transcriptomic heterogeneity of multifocal lesions on metastatic lesions. Multiple (multifocal/multicentric) breast carcinomas, especially when occurring in the same breast, represent a real challenge for both pathologists and clinicians in terms of identifying the cellular origin and the best therapeutic choice. This project has the potential to identify genetic/transcriptomic differences existing between several lesions constituting multifocal breast cancers, which in the routine clinical practice are usually considered to be homogeneous among them. We foresee validating significant results in a larger series of patients and this, in turn, could have a remarkable impact on the treatment and clinical management of multifocal breast cancers. Indeed, we hope to provide some evidence whether or not each focus matters in multifocal and multicentric breast cancer to define the adequate therapeutic approach, especially in the context of targeted therapies. The work to be done at Sanger will be target gene screen pooling of 1400 samples. Illumina HiSeq 2000; 908
EGAD00001000732 RNA sequencing to validate findings of somatic pseudogenes acquired during cancer development Illumina HiSeq 2000; 3
EGAD00001000747 Genomic libraries will be generated from total genomic DNA derived from 4000 samples with Acute Myeloid Leukaemia. Libraries will be enriched for a selected panel of genes using a bespoke pulldown protocol. 64 Samples will be individually barcoded and subjected to up to one lanes of Illumina HiSeq. Paired reads will be mapped to build 37 of the human reference genome to facilitate the characterisation of known gene mutations in cancer as well as the validation of potentially novel variants identified by prior exome sequencing. Illumina HiSeq 2000; 2734
EGAD00001000812 Sequencing of 350 cancer genes in BC samples from patients treated with either Epirubicin or Paclitaxel monotherapy in the neoadjuvant setting. Illumina HiSeq 2000; 364
EGAD00001000825 This study aims to define the landscape of somatic mutations in sun exposed human skin by deep sequencing, analyse their frequency and use the data to infer the effect of mutations on proliferating cell behaviour. The frequency of each mutation will reflect the size of the clone of cells in the tissue sample. By analyzing small samples, clones with as few as 100 cells will be detectable. Allele frequency distributions for each mutation will be used to infer cell fate using published methods (Klein et al. 2010). This study will shed unprecedented light on the early clonal events that lead to the emergence of cancer. Illumina HiSeq 2000; 454
EGAD00001000824 RNA sequencing will be undertaken to reconstruct rearrangements at level of transcription to determine pathogenomic genomic events in chondromyxoid fibroma. Illumina HiSeq 2000; 1
EGAD00001000847 Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, leukemia predisposition, and skeletal abnormalities. We aim to characterise the structural effects of SDS in patients with this disorder by exome sequencing. Illumina HiSeq 2000; 2
EGAD00001000848 To evaluate the presence of mutations in frequently mutated genes in MPN by performing targeted resequencing of a selected gene panel comprising of 111 genes across 40 samples with MPN. Illumina MiSeq; 48
EGAD00001000869 It is the ambition of the team formed by members of the Netherlands Cancer Institute (NKI) and the Cancer Genome Project at the Wellcome Trust Sanger Institute (WTSI) to unravel the genomic and phenotypic complexity of human cancers in order to identify optimal drug combinations for personalized cancer therapy. Our integrated approach will entail (i) deep sequencing of human tumours and cognate mouse tumours; (ii) drug screens in a 1000+ fully characterized tumour cell line panel; (iii) high-throughput in vitro and in vivo shRNA and cDNA drug resistance and enhancement screens; (iv) computational analysis of the acquired data, leading to significant response predictions; (v) rigorous validation of these predictions in genetically engineered mouse models and patient-derived xenografts. This integrated effort is expected to yield a number of combination therapies and companion-diagnostics biomarkers that will be further explored in our existing clinical trial networks. Illumina HiSeq 2000; 62
EGAD00001000868 FFPE CPA accreditation of genome-scale sequencing in routinely collected formalin-fixed paraffin-embedded (FFPE) cancer specimens versus matched fresh-frozen samples using targeted pulldown capture prior to Illumina sequencing. Illumina HiSeq 2000; 60
EGAD00001000872 These samples are to be analysed with the CGP Developed cancer panel and the results will be compared with WGS data from 4 different comercial providers. Illumina HiSeq 2500; 8
EGAD00001000871 The purpose of this study is to sequence 500 known cancer genes in 960 newly diagnosed high risk breast cancer patients treated with current standard of care therapies and trastuzumab, for somatic alteration and copy number changes. We will be using next gen sequencing technology to determine the prognostic relevance of these somatic genetic alterations and of teh low frequency events to determine if they are associated with trastuzumab benefit or HER2 positive breast cancer, i.e. treatment interaction. The samples will be analysed adn correlated with clinical variables including outcome. Illumina HiSeq 2000; 993
EGAD00001000870 Testing logistics and infrastructure of molecular screening program. Core biopsies taken from invasive recurrent or metastatic breast cancer to evaluate and identify molecular traits rendering them suitable for clinical trials Illumina HiSeq 2500; 52
EGAD00001000875 The CRO7 clinical trial recruited patients with clinically operable rectal adenocarcinoma. Patients were randomized to either pre-operative short course surgery followed by chemo-radiotherapy only in those patients at high risk of local relapse. Patients in both arms the received standard %-FU based adjuvant chemotherapy as per local policy. We intend to use FFPE derived DNA from the primary tumours to identify patterns of mutations or copy number alterations that are predictive of local or distant relapse. Illumina HiSeq 2000; 330
EGAD00001000898 Cancers are ecosystems of genetically related clones, competing across space and time for limited resources. To understand the clonal structure of primary breast cancer, we applied genome and targeted sequencing to 295 samples from 49 patients’ tumors. The extent of subclonal diversification varied considerably among patients and encompassed many spatial patterns, including local growth, intraductal dissemination and clonal intermixture. Landmarks of disease progression, such as acquiring invasive or metastatic potential, arose within detectable subclones of antecedent lesions, suggesting that subclonal mutations could be relevant if actionable. No defined temporal order of mutation was evident, with the commonest genes, including PIK3CA, TP53, BRCA2, PTEN and MYC, mutated early in some, late in others, often exhibiting parallel evolution across subclones. Signatures of homologous recombination deficiency correlated with response to neoadjuvant chemotherapy. Thus, the interplay of mutation, growth and competition drives clonal structures of breast cancer that are complex, variable across patients and clinically relevant. Illumina HiSeq 2000; 42
EGAD00001001237 This is a pilot project to determine whether the TAPG FFPE DNA's are suitable for deep sequencing. If successful an investigation of SNP distribution in a larger cohort will follow. Illumina HiSeq 2000; 15
EGAD00001001265 Genomic architecture of mesothelioma parent study is project 925. This project is set up in parallel to project 925 in order to Whole genome sequence ten of the 59 tumours in that project. HiSeq X Ten; 18
EGAD00001001266 Whole genome sequencing of primary angiosarcoma HiSeq X Ten; 12
EGAD00001001267 Anaplastic meningiomas are a rare, malignant variant of meningioma. At present there is no effective treatment for this cancer. The aim of the study is to identify somatic mutations in anaplastic meningiomas. We plan to sequence a set of 500 known cancer genes in 50 anaplastic meningioma and corresponding peripheral blood DNA samples. Bioinformatics will be used to analyse the results to assess the probability of these mutations being causal and so likely of critical importance for the tumour growth. Identification of these mutations will guide selection of appropriate compounds to effectively treat the disease. HiSeq X Ten; 60
EGAD00001001271 Around 50 samples of pre-invasive lung cancer lesions showing subsequent clinical and pathological progression or regression HiSeq X Ten; 50
EGAD00001001242 Pilot study to set up sequencing protocols for targeted pulldown methylation profiling Illumina MiSeq; 2
EGAD00001001236 Targetted capture and resequencing of 94 known myeloid genes across MPN trials (PT1 and Voriconazole study) and other MPN samples. Illumina HiSeq 2000; 1860
EGAD00001000947 Genomic libraries (500 bps) will be generated from total genomic DNA derived from Colorectal cancer patients and subjected to short paired end sequencing on the llumina platform. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions. Illumina HiSeq 2000; 45
EGAD00001000948 A comparison of the somatic variation present in a primary colorectal tumour and three different liver metastases from the same patient. Illumina HiSeq 2000; 6
EGAD00001000965 Cancers are ecosystems of genetically related clones, competing across space and time for limited resources. To understand the clonal structure of primary breast cancer, we applied genome and targeted sequencing to 295 samples from 49 patients’ tumors. The extent of subclonal diversification varied considerably among patients and encompassed many spatial patterns, including local growth, intraductal dissemination and clonal intermixture. Landmarks of disease progression, such as acquiring invasive or metastatic potential, arose within detectable subclones of antecedent lesions, suggesting that subclonal mutations could be relevant if actionable. No defined temporal order of mutation was evident, with the commonest genes, including PIK3CA, TP53, BRCA2, PTEN and MYC, mutated early in some, late in others, often exhibiting parallel evolution across subclones. Signatures of homologous recombination deficiency correlated with response to neoadjuvant chemotherapy. Thus, the interplay of mutation, growth and competition drives clonal structures of breast cancer that are complex, variable across patients and clinically relevant. Illumina HiSeq 2000; 331
EGAD00001001123 Deep sequencing of two skin biopsies to study the landscape of somatic mutations in human adult tissues. Illumina HiSeq 2000; 2
EGAD00001001330 In this experiment we have sequenced tumour normal pairs from patients presenting with CRC who have a prior history of inflammatory bowel disease. The idea is to identify driver mutations, new genes and novel pathways associated with the development of these malignancies. Illumina HiSeq 2000; 70
EGAD00001001017 DNA extracted from multiple biopsies taken from different areas of primary lung tumours will be subjected to targeted re-sequencing and analysed in order to assess intra-tumour heterogeneity with respect to mutations in a selection of cancer related genes. Illumina HiSeq 2000; 31
EGAD00001001018 The samples will be sequenced for a targeted panel of cancer relevant genes (n ~ 370) and analysed for somatic mutations. This dataset contains all the data available for this study on 2014-09-24 Illumina HiSeq 2000; 374
EGAD00001000998 Targeted capture of exonic and intronic regions of interest for the study of genomic alterations in multiple myeloma. Illumina HiSeq 2000; 24
EGAD00001001889 ***THIS DATA CAN ONLY BE USED FOR NON-COMMERCIAL CANCER RESEARCH*** Sequencing of organoid cell lines derived from oesophageal tumour sections taken from patients diagnosed with primary oesophageal cancer who underwent tumour resection surgery. HiSeq X Ten; 9
EGAD00001001898 The study will investigate serial samples from the same patient taken at the time of MGUS or SMM diagnosis, and later at the time of evolution towards MM. Samples will be sequenced by whole genome along with a matched normal to obtain the highest possible amount of information toinvestigate genomic changes at disease evolution. This dataset contains all the data available for this study on 2016-01-27. HiSeq X Ten; 131
EGAD00001001028 DNA belonging to 16 tumour/normal samples were treated with bisulfite, then up to 5 different bisulfite PCRs were performed in each one of the samples. Amplicons form the same sample were pooled and submitted to sequencing on a MiSeq platform. Illumina MiSeq; 18
EGAD00001001014 Illumina HiSeq 2000; 2597
EGAD00001001015 Illumina HiSeq 2000; 76
EGAD00001000888 NSCLC WGS. AB 5500 Genetic Analyzer; 4
EGAD00001000889 NSCLC targeted. Ion Torrent PGM; 4
EGAD00001001039 Genomic characterisation of a large series of cancer cell lines. Illumina HiSeq 2000; 1072
EGAD00001000990 mRNA-Seq on total RNA from primary osteoblastomas and phosphaturic mesenchymal tumours, focussing on fusion transcript expression Illumina HiSeq 2000; 11
EGAD00001000980 This study involves a forward genetic screen to identify common insertion sites in drug resistant clones. We will be utilising piggybac transposon systems in order to generate multiple drug resistant clones in a range of human cancer cell lines. Illumina MiSeq; 144
EGAD00010000644 Affymetrix SNP6.0 cancer cell line exome sequencing data 1022
EGAD00001001046 We propose to biopsy 20 consented BRAF mutant melanoma patients at Addenbrooke's Hospital pre-treatment with vemurafenib and also upon the development of resistant disease, with the aim of using exome sequence and SNP6 data to identify novel sequence variants and copy number alterations that can be used to validate observed resistance mechanisms in our cell line models and also to use these models to inform as to likely candidate small molecule inhibitors to overcome resistance and that could be tested in the clinical trial setting. Illumina HiSeq 2000; 33
EGAD00001001062 Patient (who has had multiple malignancies) has previously been found to harbour a pathogenic p53 variant which is probably mosaic. This finding is based on exome sequencing performed elsewhere. In this study we will resequence the locus in question to ascertain whether the variant is indeed mosaic. Illumina MiSeq; 4
EGAD00001001063 Chondromxoid fibroma is a benign tumour of bone with unknown underlying pathogenesis. To determine pathognomic genomic event in chondromyxoid fibroma whole genome sequencing will be undertaken to reconstruct rearrangements and find underlying mutations. Illumina HiSeq 2000; 2
EGAD00001001061 This experiment is to inform us of the validity of using pre-made library material to perform a bespoke pulldown experiment to validate the mutations found between the whole genome sequencing of the DNA from the same individuals cancer and normal material. This is to identify the valid and informative mutations in cancer genomes. Illumina MiSeq; 4
EGAD00001001090 This study aims to define the landscape of somatic mutations in sun exposed human skin by deep sequencing, analyse their frequency and use the data to infer the effect of mutations on proliferating cell behaviour. The frequency of each mutation will reflect the size of the clone of cells in the tissue sample. By analyzing small samples, clones with as few as 100 cells will be detectable. Allele frequency distributions for each mutation will be used to infer cell fate using published methods (Klein et al. 2010). This study will shed unprecedented light on the early clonal events that lead to the emergence of cancer. Illumina HiSeq 2000; 166
EGAD00001000894 SPECTA comprises a network of participating European clinical sites and NGS screening platforms that can screen individual patients for multiple molecular targets and potentially allow the design of trials that will match the specific biology of the diseases affecting specific patients with cancer. Illumina HiSeq 2500; 64
EGAD00001001122 FFPE normal panel generation for use with V3 cancer panel 0618521 Illumina HiSeq 2000; 94
EGAD00001001215 Targeted sequencing follow-up of genomic lesions in multiple myeloma. Illumina HiSeq 2000; 424
EGAD00001002065 Cetuximab is a targeted monoclonal antibody against the epidermal growth factor receptor (EGFR) which is used therapeutically for the treatment of KRAS wild-type colorectal cancer (CRC). The Cetuximab sensitive KRAS wild-type CRC cell line NCI-H508 has been treated with a fixed concentration of ENU for 24 hours and then selected with Cetuximab until drug resistant clones were ready to be picked and grown up as sub-clones of the parental cell line. These will have genes causally implicated in cancer sequenced to identify common point mutations in multiple independently derived drug resistant clones as a forward genetic screen for mechanisms of resistance to Cetuximab in CRC Illumina HiSeq 2500; 50
EGAD00001001375 Samples will be from the BRF113683 (BREAK-3) study which is a Phase III Randomized, Open-label Study Comparing GSK2118436 to Dacarbazine (DTIC) in Previously Untreated Subjects With BRAF Mutation Positive Advanced (Stage III) or Metastatic (Stage IV) Melanoma (n=250 enrolled) *NGS [Agilent capture (Sanger V2 panel): 360 genes and 20 gene fusions; Illumina HiSEQ Sequencing] *CNV: [via NGS or Affy SNP 6.0 or Illumina Omni (TBD)] Bioinformatics: Analysis will be performed using core Sanger informatics pipelines similar to those previously described (Papaemmanuil E et al. (2013) Blood. 22:3616 -3627). Briefly, copy number analysis will be performed using the ASCAT algorithm, and base substitutions, small insertions and deletions using the CAVEMAN and Pindel algorithms, respectively. Statistical approaches including generalized linear models will be used to predict clinical variables such as maximum clinical response and duration of response using genetic data. Sanger and EBI to conduct analysis; Raw data and correlation with clinical endpoints to be analyzed by both EBI/Sanger and GSK (unique pipeline analyses to increase call confidence) Illumina HiSeq 2500; 169
EGAD00001001389 Genome wide CRISPR screen was performed to find resistance to targeted drugs for melanoma and lung Illumina HiSeq 2500; 15
EGAD00001001426 Systematic next generation sequencing efforts are beginning to define the genomic landscape across a range of primary tumours, but we know very little of the mutational evolution that contributes to disease progression. We therefore propose to obtain a comprehensive description of genomic, transcriptomic and epigenomic changes in a cohort of matched primary and metastatic colorectal cancers, and additionally to explore the extent to which those mutations identified as recurrent in the metastatic setting are able to subvert normal biological processes using both genetically engineered mouse models and established cancer cell lines. This study will enable us to define to what extent primary tumour profiling can capture the biological processes operative in matched metastases as well as the significance of intratumoural heterogeneity. This dataset contains all the data available for this study on 2015-07-02. Illumina HiSeq 2000; 446
EGAD00001001427 Targeted cancer gene sequencing of samples enrolled in the SSGXVIII trial from Finland. Illumina HiSeq 2000; 312
EGAD00001001428 Identification of human deubiquitylating enzymes whose knock out result in hypersensitivity to DNA damaging agents, by comparing the sequence reads of 'barcode region' from mixed cell culture. Illumina HiSeq 2000; 6
EGAD00001001429 Profiling subclonal architecture and phylogeny in tumors by whole-genome sequence data mining and single-cell genome sequencing HiSeq X Ten; 2
EGAD00001001430 Investigation into causal genes underlying anaplastic meningioma Illumina HiSeq 2000; 73
EGAD00001001445 Deep sequencing of melanoma for driver mutations Illumina MiSeq; 3
EGAD00001001446 Genomic and transcriptomic characterization of drug-resistant colon cancer stem cell lines. Illumina HiSeq 2000; 4
EGAD00001001447 Whole genome sequencing of single cell derived organoids from normal colon tissue and colorectal cancer. HiSeq X Ten; 19
EGAD00001001448 Testing the feasibility of genome-scale sequencing in routinely collected formalin-fixed paraffin-embedded (FFPE) cancer specimens versus matched fresh-frozen samples using targeted pulldown capture prior to Illumina sequencing. Illumina MiSeq; 11
EGAD00001001450 This study is to ascertain whether it is feasible to extract single cell from a tumour, perform amplification, generate a library and sequence a targeted pulldown. Illumina HiSeq 2000; 3
EGAD00001001458 Whole genome sequencing of EBV-transformed B cells in order to determine whether EBV induction of activation-induced cytidine deaminase (AID) produces genome-wide mutations and/or chromosomal rearrangements. HiSeq X Ten; 12
EGAD00001001459 Transcriptome sequencing of tumour tissue, adjacent normal tissue and derived organoids/tumoroids from colorectal cancer. This dataset contains all the data available for this study on 2015-08-05. Illumina HiSeq 2000; 76
EGAD00001001600 PCR and MiSeq validation for early embryonic substitution candidates from 400 Breast cancer patients. This dataset contains all the data available for this study on 2015-09-03. Illumina MiSeq; 2
EGAD00001001629 Whole-genome somatic rearrangement and point mutation analysis in cell lines with induced telomere fusions. HiSeq X Ten; 20
EGAD00001001845 Leeds Melanoma Cohort Illumina HiSeq 2000; 16
EGAD00001001846 2 BRAFV600E cell lines that have been made resistance to 1. the BRAF inhibitor PLX4720 and 2. the combination therapy of dabrafenib and trametinib seem to have a internal duplication in the kinase domain. We would like to know if this is caused by a translocation. HiSeq X Ten; 4
EGAD00001001879 A pilot to establish the feasability of using a custom Agilent targeted pulldown of 110 genes implicated in colorectal tumourigensis to sequence for driver mutations in a set of 30 FFPE colorectal adenomas. If successful, we propose to sequence an additional 350 adenomas as part of a MRC research study in order to define the pattern of driver mutations across the spectrum of pathological subtypes including coventional adenomas, serrated adenomas and hyperplastic polyps Illumina HiSeq 2000; 30
EGAD00001001947 Cetuximab is a targeted monoclonal antibody against the epidermal growth factor receptor (EGFR) which is used therapeutically for the treatment of KRAS wild-type colorectal cancer (CRC). The Cetuximab sensitive KRAS wild-type CRC cell line NCI-H508 has been treated with a fixed concentration of ENU for 24 hours and then selected with Cetuximab until drug resistant clones were ready to be picked and grown up as sub-clones of the parental cell line. These will have genes causally implicated in cancer sequenced to identify common point mutations in multiple independently derived drug resistant clones as a forward genetic screen for mechanisms of resistance to Cetuximab in CRC. Illumina HiSeq 2000; 16
EGAD00001001948 Cetuximab is a targeted monoclonal antibody against the epidermal growth factor receptor (EGFR) which is used therapeutically for the treatment of KRAS wild-type colorectal cancer (CRC). The Cetuximab sensitive KRAS wild-type CRC cell line NCI-H508 has been treated with a fixed concentration of ENU for 24 hours and then selected with Cetuximab until drug resistant clones were ready to be picked and grown up as sub-clones of the parental cell line. These will have genes causally implicated in cancer sequenced to identify common point mutations in multiple independently derived drug resistant clones as a forward genetic screen for mechanisms of resistance to Cetuximab in CRC Illumina HiSeq 2000; 16
EGAD00001002051 BRAF V600E colorectal cancers do not respond to the only currently FDA approved targeted therapy for CRC. There is currently a trial underway in the UK recruiting V600E CRC patients for treatment with a triple therapy combination of Cetuximab, Trametinib and Dabrafenib. We have mutagenized a pool of V600E CRC cell lines and treated with this triple therapy to select out drug resistant clones. We will now sequence these drug resistant clones with the aim of identifying common point mutations engendering resistance to this new therapy. Illumina HiSeq 2500; 20
EGAD00001002066 KRAS mutant CRC is currently in clinical trial with a combination of a MEK and Akt inhibitor. These patients will likely develop resistance to this combination. We aim to identify the mechanisms of resistance via ENU mutagenesis, with a view to identifying additional therapeutics which have the ability to overcome this resistance. Illumina HiSeq 2500; 86
EGAD00001002015 The use of reference DNA standards generated from cancer cell lines sequenced in the Cancer Genome Project to establish the sensitivity, specificity, accuracy and reproducibility of the WTSI GCLP sequencing pipeline Illumina HiSeq 2000; 57
EGAD00001001395 Background: Invasive lobular breast cancer (ILBC) is the second most common histological subtype after ductal breast cancer (IDBC). In spite of significant clinical and pathological differences, ILBC is still treated as IDBC. Here, we aimed at identifying recurrent genomic alterations in ILBC with potential clinical implications. Methods: Starting from 630 ILBC primary tumors with a median follow up of 10 years, we interrogated oncogenic substitutions and indels of 360 cancer genes and genome-wide copy number alterations in 413 and 170 ILBC samples, respectively, and correlated those findings with clinical, pathological, and outcome features. The Cancer Genome Atlas database was used for comparison of frequency estimates. Results: Besides the high mutation frequency of CDH1 in 65% of the tumors, alterations in one of the three key genes of the PI3K pathway, PIK3CA, PTEN and AKT1, were present in more than half of the cases. ERBB2 and ERBB3 were mutated in 5.1 and 3.6% of the tumors. FOXA1 mutations and ESR1 copy number gains were detected in 9% and 25% of the samples. All these alterations were more frequent in ILBC than IDBC. The histological diversity of ILBC was associated with specific genomic alterations, such as enrichment for ERBB2 mutations in the mixed, non-classic subtype, and for ARID1A mutations and ESR1 gains in the solid subtype. Finally, ERBB2 and AKT1 mutations were associated with short-term risk of relapse, and chromosome 1q and 11p gain with increased and decreased breast cancer free survival, respectively. Conclusion: ERBB2, ERBB3 and AKT1 mutations represent high prevalence therapeutic targets in ILBC. FOXA1 mutations and ESR1 gains urgently deserve dedicated clinical investigation, especially in the context of endocrine treatment. Illumina HiSeq 2000; 541
EGAD00001002236 The disordered transcriptomes of cancer encompass direct effects of somatic mutation on transcription; co-ordinated secondary alterations in transcriptional pathways; and increased transcriptional noise. To catalogue the rules governing how somatic mutation Overall, 59% of 6980 exonic substitutions were expressed. Compared to other classes, nonsense mutations showed lower expression levels than expected with patterns characteristic of nonsense-mediated decay. 14% of 4234 genomic rearrangements caused transcriptional abnormalities, including exon skips, exon reusage, fusion transcripts and premature poly-adenylation. We found productive, stable transcription from sense-to-antisense gene fusions and gene-to-intergenic rearrangements, suggesting that these mutation classes may drive more transcriptional disruption than previously suspected. Systematic integration of transcriptome with genome data therefore reveals the rules by which transcriptional machinery interprets somatic mutation. Illumina HiSeq 2000; 32
EGAD00001002237 The disordered transcriptomes of cancer encompass direct effects of somatic mutation on transcription; co-ordinated secondary alterations in transcriptional pathways; and increased transcriptional noise. To catalogue the rules governing how somatic mutation Overall, 59% of 6980 exonic substitutions were expressed. Compared to other classes, nonsense mutations showed lower expression levels than expected with patterns characteristic of nonsense-mediated decay. 14% of 4234 genomic rearrangements caused transcriptional abnormalities, including exon skips, exon reusage, fusion transcripts and premature poly-adenylation. We found productive, stable transcription from sense-to-antisense gene fusions and gene-to-intergenic rearrangements, suggesting that these mutation classes may drive more transcriptional disruption than previously suspected. Systematic integration of transcriptome with genome data therefore reveals the rules by which transcriptional machinery interprets somatic mutation. Illumina HiSeq 2000;ILLUMINA, Illumina Genome Analyzer II;ILLUMINA 59
EGAD00001002229 Detection of BAP1 mutations in DNA from uveal melanoma and mesothelioma samples. Illumina HiSeq 2000; 22
EGAD00001001208 Targeted capture of cancer gene panel bait set in single cell derived organoids from colon tissue and colorectal cancer from 1 patient. Illumina HiSeq 2000;, Illumina HiSeq 2500; 105
EGAD00001002232 Mapping genetic evolution of pancreatic cancer precursor lesions such as IPMNs and PanINs. Illumina HiSeq 2000; 20
EGAD00001002234 This study involves mutagenizing C32, a melanoma cell line, with ENU to identify those mutations which engender resistance to a targeted treatment. Illumina HiSeq 2000; 84
EGAD00001000333 Cancer is driven by mutations in the genome. We will uncover the mutations that give rise to Ewing's sarcoma, a bone tumour that largely affects children. We will use second generation Illumina massively parallel sequencing, and bespoke software, to characterise the genomes and transcriptomes of Ewing,s sarcoma tumours. Illumina HiSeq 2000; 58
EGAD00001001041 Comparison of genomic rearrangements and DNA methylation patterns between different foci of multiple synchronous (multifocal and multicentric) invasive breast cancers. Illumina Genome Analyzer II;, Illumina HiSeq 2000; 305
EGAD00001002698 Recurrent breast cancer is almost universally fatal. We characterize 170 patients locally relapsed or distant metastatic cancers using massively parallel sequencing. We identify that the relapse-seeding clone disseminates late from the primary tumor. TP53 and AKT1 appear to be enriched in ER-positive cancers predisposed to relapse. Mutation acquisition continues at relapse as the same mutation signatures continue to operate and new signatures, such as that caused by radiotherapy appear de novo. In 49% of cases we identify drivers mutations private to the relapse and these are sampled from a wider range of cancer genes, including SWI-SNF complex and JAK-STAT signaling. Illumina MiSeq;ILLUMINA, Illumina HiSeq 2000;ILLUMINA, Illumina HiSeq 2500;ILLUMINA 387
EGAD00001002696 Recurrent breast cancer is almost universally fatal. We characterize 170 patients locally relapsed or distant metastatic cancers using massively parallel sequencing. We identify that the relapse-seeding clone disseminates late from the primary tumor. TP53 and AKT1 appear to be enriched in ER-positive cancers predisposed to relapse. Mutation acquisition continues at relapse as the same mutation signatures continue to operate and new signatures, such as that caused by radiotherapy appear de novo. In 49% of cases we identify drivers mutations private to the relapse and these are sampled from a wider range of cancer genes, including SWI-SNF complex and JAK-STAT signaling. HiSeq X Ten;ILLUMINA, Illumina HiSeq 2000;ILLUMINA 60
EGAD00001003217 Targeted resequencing at high depth (21 genes, 9 chromosomal regions): at least 4 FFPE samples per case and matched germline DNA: * 100 cases with detailed outcome data, including 15 cases with tumour relapse (515 samples) * 40 cases with matched pre-chemotherapy biopsies (240 samples) * 50 nephrogenic rests matched to above cases (50 samples) We expect a proportion (possibly 10%) of cases to be mutationally silent on the above studies, and propose to subsequently carry out integrated whole-genome, methylome and transcriptome studies on matched frozen tissue from these cases Illumina HiSeq 2500;ILLUMINA 35
EGAD00001003216 Whole genome sequencing of tumour normal pairs of human undifferentiated sarcomas. HiSeq X Ten;ILLUMINA 98
EGAD00001003239 This study involves mutagenizing C32, a melanoma cell line, with ENU to identify those mutations which engender resistance to a targeted treatment. Illumina HiSeq 2000;ILLUMINA 80
EGAD00001003240 Study of cell lineage and embryogenesis using biopsy samples from sites across the whole body (post mortem). Sample donors are recruited sensitively through the Phoenix study and consent to samples being taken after their death for both the Phoenix study and this WTSI study. HiSeq X Ten;ILLUMINA 33
EGAD00001003242 This study comprises of three different datasets. 1) 57 samples from the 1243 canapps cell line study,2) 91 FFPE normal samples and 3) 87 samples from the SCORT WS2 dataset. The aim is to sequence these 235 samples in order to test the new V2 Colorectal bait design. Illumina HiSeq 2000;ILLUMINA 92
EGAD00001003248 A BRAF V600E colorectal organoid which is sensitive to MAP kinase inhibition was mutagenised with the chemical mutagen ENU and then drug selected using a combination of Trametinib, Dabrafenib and Cetuximab. Single cell derived organoids were then manually picked and expanded in drug. Resistance was confirmed in a 14 day assay and DNA was collected. These then underwent targeted amplicon-based sequencing to confirm candidate resistance effectors from a screen in 2 2D BRAF V600E colorectal cell lines. Pools of resistant clones were also sequenced. Illumina MiSeq;ILLUMINA 36
EGAD00001003252 Sequencing of drug resistant organoids Illumina HiSeq 2000;ILLUMINA 36
EGAD00001003255 Transcriptome of anaplastic meingiomas Illumina HiSeq 2500;ILLUMINA 34
EGAD00001003253 Targeted gene screen of cell line tumour samples for testing the new V2 Colorectal gene panel. Illumina HiSeq 2000;ILLUMINA 57
EGAD00001003254 R&D project to develop low input library construction methods. Illumina HiSeq 2500;ILLUMINA 12
EGAD00001000205 BRAF and MEK resistant cell line clones Illumina HiSeq 2000; 3
EGAD00001003309 The study will investigate serial samples from the same patient taken at the time of MGUS or SMM diagnosis, and later at the time of evolution towards MM. Samples will be sequenced by whole genome along with a matched normal to obtain the highest possible amount of information toinvestigate genomic changes at disease evolution. This dataset contains all the data available for this study on 2017-04-27. HiSeq X Ten;ILLUMINA 139
EGAD00001003320 Transcriptome sequencing of tumour tissue, adjacent normal tissue and derived organoids/tumoroids from colorectal cancer This dataset contains all the data available for this study on 2017-05-04. Illumina HiSeq 2000;ILLUMINA, Illumina HiSeq 2500;ILLUMINA 106
EGAD00001003321 Systematic next generation sequencing efforts are beginning to define the genomic landscape across a range of primary tumours, but we know very little of the mutational evolution that contributes to disease progression. We therefore propose to obtain a comprehensive description of genomic, transcriptomic and epigenomic changes in a cohort of matched primary and metastatic colorectal cancers, and additionally to explore the extent to which those mutations identified as recurrent in the metastatic setting are able to subvert normal biological processes using both genetically engineered mouse models and established cancer cell lines. This study will enable us to define to what extent primary tumour profiling can capture the biological processes operative in matched metastases as well as the significance of intratumoural heterogeneity. This dataset contains all the data available for this study on 2017-05-04. Illumina HiSeq 2000;ILLUMINA 523
EGAD00001003330 The samples will be sequenced for a targeted panel of cancer relevant genes (n ~ 370) and analysed for somatic mutations. This dataset contains all the data available for this study on 2017-05-11. Illumina HiSeq 2000;ILLUMINA 416
EGAD00001003332 PCR and MiSeq validation for early embryonic substitution candidates from 400 Breast cancer patients This dataset contains all the data available for this study on 2017-05-11. Illumina MiSeq;ILLUMINA 4
EGAD00001003334 Targeted exome sequencing of patient derived xenografts from primary colorectal tumours and liver metastases. This dataset contains all the data available for this study on 2017-05-11. Illumina HiSeq 2000;ILLUMINA 573
EGAD00001003425 A EGFR mutant NSCLC cell line which is sensitive to AZD9291 inhibition was mutagenised with the chemical mutagen ENU and then drug selected using a AZD9291. Single cell derived colonies were then manually picked and expanded in drug. Resistance was confirmed in a 14 day assay and DNA was collected. These then underwent targeted amplicon-based sequencing to confirm candidate resistance effectors hypothesised from currently available literature. This dataset contains all the data available for this study on 2017-07-05. Illumina MiSeq;ILLUMINA 177
EGAD00001003445 Clear cell renal cancer is characterized by near-universal loss of the short arm of chromosome 3 (3p). This event arises through unknown mechanisms, but critically results in the loss of several tumor suppressor genes. We analyzed whole genomes from 95 biopsies across 33 patients with clear cell renal cancer (ccRCC) recruited into the Renal TRACERx study. We find novel hotspots of point mutations in the 5'-UTR of TERT, targeting a MYC-MAX repressor, that result in telomere lengthening. The most common structural abnormality generates simultaneous 3p loss and 5q gain (36% patients), typically through chromothripsis. Using molecular clocks, we estimate this occurs in childhood or adolescence, generally preceding emergence of the most recent common ancestor by years to decades. Similar genomic changes recent common ancestor by years to decades. Similar genomic changes are seen in inherited kidney cancers. Modeling differences in age-incidence between inherited and sporadic cancers suggests that the number of cells with 3p loss capable of initiating sporadic tumors is no more than a few hundred. Targeting essential genes in deleted regions of chromosome 3p could represent a potential preventative strategy for renal cancer. HiSeq X Ten;ILLUMINA 164