7790 results for "canc*"

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• Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers

  Infiltration of human cancers by T cells is generally interpreted as a sign of immune recognition, and there is a growing effort to reactivate dysfunctional T cells at such tumor sites. However, these efforts only have value if the intratumoral T cell receptor (TCR) repertoire of such cells is intrinsically tumor-reactive, and this has not been established in an unbiased manner for most human cancers. To address this issue, we analyzed the intrinsic tumor-reactivity of the intratumoral TCR repertoire of CD8+ T cells in ovarian and colorectal cancer – two tumor types for which T cell infiltrates form a positive prognostic marker. Data obtained demonstrate that a capacity to recognize autologous tumor is limited to approximately 10% of intratumoral CD8+ T cells. Furthermore, in two out of four patient samples tested, no tumor-reactive TCRs were identified, despite infiltration of their tumors by T cells. These data indicate that the intrinsic capacity of intratumoral T cells to recognize adjacent tumor tissue can be rare and variable, and suggest that clinical efforts to reactivate intratumoral T cells will benefit from approaches that simultaneously increase the quality of the intratumoral TCR repertoire.

  Study EGAS00001003119

• Renal_Follow_Up_Series

  This study's purpose is to use data generated in Renal whole genome and exome Cancer sequencing to target specific areas in multiple other Renal Cancer samples. These areas will then be subjected to bespoke pull downs, tagged and then pool the resultant amplicons. These amplicons will then be sequenced. This is hoped to show the prevalence of previous findings in multiple individuals in a high throughput method.

  Study EGAS00001000095

• The University of Hong Kong Gastric Cancer Organoids RHO Signaling Study

  Objective: Cell-cell (CC) and cell-matrix (CM) adhesions are essential for epithelial cell survival, yet dissociation-induced apoptosis is frequently circumvented in malignant cells. Design: We explored CC and CM dependence in 58 gastric cancer (GC) organoids by withdrawing either ROCK inhibitor, matrix, or both, to evaluate their tumorigenic potential in terms of apoptosis resistance, correlation with oncogenic driver mutations and clinical behaviour. We performed mechanistic studies to determine the role of diffuse-type GC drivers: ARHGAP fusions, RHOA, and CDH1, in modulating CC (CCi) or CM (CMi) adhesion independence. Results: 97% of the tumour organoids were CMi, 66% were CCi and 52% were resistant to double withdrawal (CCi/CMi), while normal organoids were neither CMi nor CCi. Clinically, the CCi/CMi phenotype was associated with an infiltrative tumour edge and advanced tumour stage. Moreover, the CCi/CMi transcriptome signature was associated with poor patient survival when applied to 3 public GC datasets. CCi/CMi and CCi phenotypes were enriched in diffuse-type GC organoids, especially in those with oncogenic driver perturbation of RHO signalling via RHOA mutation or ARHGAP fusions. Inducible knockout of ARHGAP fusions in CCi/CMi tumour organoids led to re-sensitization to CC/CM dissociation-induced apoptosis, upregulation of focal adhesion and tight junction genes, partial reversion to a more normal cystic phenotype, and inhibited xenograft formation. Normal gastric organoids engineered with CDH1 or RHOA mutations became CMi or CCi, respectively. Conclusions: The CCi/CMi phenotype has a critical role in malignant transformation and tumour progression, offering new mechanistic information on RHO-ROCK pathway inhibition that contributes to GC pathogenicity.

  Study EGAS00001006252

• Whole exome DNA sequence profiling of spatial biopsies of high grade serous epithelial ovarian cancer

  The study aims at dissecting the heterogeneity across multiple biopsies of high grade serous epithelial ovarian cancer (HGS-EOC) through a comprehensive characterization of variants and structural changes at the whole exome level. To this aim, the study uses samples from multiple bioptic sites taken from eight HGS-EOC patients.

  Study EGAS00001003048

• Mutational_Analysis_of_Colorectal_PDX_models

  Targeted exome sequencing of patient derived xenografts from primary colorectal tumours and liver metastases.

  Study EGAS00001001171

• The polarity and specificity of antiviral T lymphocyte responses determine susceptibility to SARS-CoV-2 infection in cancer patients and healthy individuals.

  The goal of this study was to identify immune correlates of clinical protection against SARS-CoV-2 infection.

  Study EGAS00001005985

• Whole Exome Sequencing of 60 tumor/normal matched liver Cancers (HCC)

  The French ICGC project on liver tumors is coordinated by Pr Jessica Zucman-Rossi and funded by Inca (French Institute for Cancer). The aim of the present project is to identify the catalog of somatic and germline mutations in liver tumors using whole genome (WGS) and whole exome sequencing (WGS), integrated with DNA methylation and RNA sequencing (RNA-seq) data. The present series corresponds to 60 whole exome tumor/normal pairs with matched RNA-seq. Hepatocellular carcinoma (HCC) accounts for more than 90% of liver cancers, and is a major health problem. It is the 3rd cause of cancer-related mortality. Advances in genomic analyses have formed a comprehensive understanding of different underlying pathobiological layers resulting in hepatocarcinogenesis. Thus, the development of next-generation sequencing technologies has made it possible to generate more comprehensive catalogues of somatic alteration events (single nucleotide substitutions, structural variations, and epigenetic changes) in liver cancer genome than ever before.

  Study EGAS00001003063

• RNA-seq of Glioblastoma stem cells

  Chromatin accessibility discriminates stem from mature cell populations, enabling the identification of primitive stem-like cells in primary tumors, such as Glioblastoma (GBM) where self-renewing cells driving cancer progression and recurrence are prime targets for therapeutic intervention. We show, using single-cell chromatin accessibility, that primary GBMs harbor a heterogeneous self-renewing population whose diversity is captured in patient-derived glioblastoma stem cells (GSCs). In depth characterization of chromatin accessibility in GSCs identifies three GSC states: Reactive, Constructive, and Invasive, each governed by uniquely essential transcription factors and present within GBMs in varying proportions. Orthotopic xenografts reveal that GSC states associate with survival, and identify an invasive GSC signature predictive of low patient survival. Our chromatin-driven characterization of GSC states improves prognostic precision and identifies dependencies to guide combination therapies.

  Study EGAS00001003070

• Molecular Signature of Saudi Thyroid Cancer Using whole exome sequencing

  In Saudi Arabia, thyroid cancer ranked second only to breast cancer among females, eleventh among males and this increased incidence is prevalent in other Gulf Council Countries also. Differentiated thyroid cancer, which includes papillary thyroid cancer (PTC) and follicular subtypes, accounts for 90% of all thyroid malignancies. Currently, there are no clinical or molecular diagnostic tools to predict recurrence and aggressiveness of a subset of PTC. With the goal of better understanding the pathobiology of thyroid carcinogenesis we will use Whole Exome Sequencing to decipher the molecular and genetic signature of Saudi PTC based on International Cancer Genome Consortium (ICGC) Guidelines. The study will provide a better understanding of PTC and should have important clinical implications in the development of new and better strategies for targeted therapeutic intervention for the treatment of Saudi Arabian PTC

  Study EGAS00001000680

• Primary breast cancers and paired brain metastases sequencing study

  Improving management of brain metastases (BM) from primary breast cancer (PBC) is a challenge in which targeted therapies play a promising role. However this approach is impaired by miss-knowledge of molecular patterns of the metastatic and drug-resistance processes.We performed a differential analysis of copy-number-alterations (CNAs) and mutations profiles by using pan-genomic array-CGH and targeted next-generation-sequencing of 494 cancer-associated genes, in a series of 14 pairs of matched PBC/BM and assessed if the observed genomic alterations may be used as a druggable agent in a clinical trial.

  Study EGAS00001003173

• Genetic_mechanisms_of_resistance_to_chemotherapy_in_breast_cancer

  Resistance towards chemotherapy is one of the main causes of treatment failure and deathamong breast cancer patients.The main objective of this project is to identify genetic mechanisms causing some breastcancer patients not to respond to a particluar type of chemotherapy (epirubicin) while otherpatients respond very well to the same treatment.In the project we will perform genome / exome sequencing of a selection of breast cancerpatients (n=30). These patients are drawn from a cohort where all patients have recievedtreatment with epirubicin monotherapy before surgical removal of a locally advanced breasttumour, and where all patients have been subjected to objective evaluation of the response tothe therapy.Subsequent to sequencing, we will analyse the data and compare with the clinical data foreach patient (object response to therapy). The main aim being to identify mutations that areassociated with resistance to epirubicin.Identification of mutations with strong predictive value, may have a direct impact on cancertreatment since it opens the possibility for genetic testing of a tumour, and desicion on whichdrug is likely to work best, prior to treatment start.

  Study EGAS00001000276

• Somatic point mutation data from microsatellite unstable colorectal cancers

  Microsatellite instability (MSI) leads to accumulation of an excessive number of mutations in the genome, mostly small insertions and deletions. MSI CRCs, however, also contain more point mutations than microsatellite stable (MSS) tumors, yet they have not been as comprehensively studied. To identify candidate driver genes affected by point mutations in MSI CRC, we ranked genes based on mutation significance while correcting for replication timing and gene expression utilizing an algorithm, MutSigCV. Somatic point mutation data from the exome kit-targeted area from 24 exome sequenced sporadic MSI CRCs and respective normals, and 12 whole genome sequenced sporadic MSI CRCs and respective normals were utilized. The top 73 genes were validated in 93 additional MSI CRCs.

  Study EGAS00001003101

• Breast_Cancer_Whole_Genome_Sequencing

  We propose to definitively characterise the somatic genetics of ER+ve, HER2-ve breast cancer through generation of comprehensive catalogues of somatic mutations in 500 cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.

  Study EGAS00001000210

• Osteosarcoma_Targeted_Sequencing_Study

  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.

  Study EGAS00001000278

• Lung_Plasma_rearrangement_screen

  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.

  Study EGAS00001000289

• Genome-wide association study of cervical cancer in East Asian populations

  The development of cervical cancer is initiated by human papillomavirus (HPV) infection, and involves both viral and host genetic factors. Genome-wide association studies (GWAS) of cervical cancer have identified associations in the HLA locus and two loci outside HLA, but the principal genes that control infection and pathogenesis have not been identified. In the present study, we performed GWAS of cervical cancer in East Asian populations, involving 2609 cases and 4712 controls in the discovery stage, 1461 cases and 3295 controls in the follow-up stage.

  Study EGAS00001003199

• Study the differences at the trascriptome level between iNKT and T cells

  Chimeric antigen receptor anti-CD19 (CAR19)-T cell immunotherapy-induced clinical remissions in CD19+ B cell lymphomas are often short-lived. We tested whether CAR19-engineering of the CD1d-restricted invariant NKT (iNKT) cells would result in enhanced anti-lymphoma activity. CAR19-iNKT cells co-operatively activated by CD1d- and CAR19-CD19-dependent interactions are more effective than CAR19-T cells against CD1d-expressing lymphomas in vitro and in vivo. The swifter in vivo anti-lymphoma activity of CAR19-iNKT cells and their enhanced ability to eradicate brain lymphomas underpinned an improved tumor-free and overall survival. CD1d transcriptional de-repression by all-trans retinoic acid results in further enhanced cytotoxicity of CAR19-iNKT cells against CD19+ chronic lymphocytic leukemia cells. Thus, iNKT cells are a highly efficient platform for CAR-based immunotherapy of lymphomas and possibly other CD1d-expressing cancers.

  Study EGAS00001003176

• Triple_Negative_Breast_Cancer_RNA_Sequencing

  We propose to definitively characterise the somatic genetics of triple negative 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.

  Study EGAS00001000377

• Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors

  Large-cell neuroendocrine lung carcinomas (LCNEC) have similarities with other lung cancers, but their precise relationship has remained unclear. We conducted comprehensive genomic (n=60) and transcriptomic (n=69) analyses of 75 LCNECs and identified two molecular subgroups: “type I LCNECs” with bi-allelic TP53 and STK11/KEAP1 alterations (37%), and “type II LCNECs” enriched for bi-allelic inactivation of TP53 and RB1 (42%). Despite sharing genomic alterations with adenocarcinomas and squamous cell carcinomas, no transcriptional relationship was found; instead LCNECs form distinct transcriptional subgroups with closest similarity to SCLC. While type I LCNECs and SCLCs exhibit a neuroendocrine profile with ASCL1high/DLL3high/NOTCHlow, type II LCNECs bear TP53 and RB1 alterations and differ from most SCLC tumors with reduced neuroendocrine markers, a pattern of ASCL1low/DLL3low/NOTCHhigh and upregulation of immune-related pathways. In conclusion, LCNECs are comprised of two molecularly defined subgroups, and distinguishing them from SCLC may allow for stratified targeted treatments for high-grade neuroendocrine lung tumors.

  Study EGAS00001000708

• ERBB2/HER2 transmembrane and juxtamembrane domain mutations in cancer

  In this study, we identified several recurrent activating HER2 somatic mutations in transmembrane and juxtamembrane domain in multiple cancers and demonstrate that patients carryingthese mutations are candidates for anti-HER2 therapy. We have also identified a germline mutation in HER2 transmembrane domain.

  Study EGAS00001003213

• Myeloproliferative_Neoplasms__MPN__Targeted_Gene_Screen

  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.

  Study EGAS00001000406

• Prostate_Cancer_Whole_Genome_Validations

  We propose to definitively characterise the somatic genetics of Prostate cancer through generation of comprehensive catalogues of somatic mutations by high coverage genome sequencing. This study will aim to validate the findings of the whole genome study by re-sequencing regions of interest using a bespoke pulldown bait. See ICGC website for more information: http://icgc.org/icgc/cgp/70/508/71331

  Study EGAS00001000427

• Meningioma_Targeted_Sequencing_Study

  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.

  Study EGAS00001000282

• X10_sequencing_of_Oesophageal_Adenocarcinoma_Organoids

  X10 Sequencing of 5 patient derived organoid cell models. Each model was derived from a piece of patient tumour taken following surgical resection of the tumour. All model derivations took place with the CGaP facility in Sanger. This PacBio data will be combined with other sequencing data in order to generate accurate reference cancer genomes.

  Study EGAS00001003264

• Harnessing_transposons_for_drug_resistance_gene_discovery_in_cancer

  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.

  Study EGAS00001000468

• Osteosarcoma_whole_genome_rearrangement_screen

  Genomic libraries (500 bps) will be generated from total genomic DNA derived from Osteosarcoma 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.

  Study EGAS00001000330

• Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer RNA-Seq

  The goal of the sequencing study was to determine the neoantigen profile of melanoma patients. We performed whole exome sequening of the tumor and respective patien matched PBMC samples (2x50nt) and RNA-sqeuencing of the tumor samples. The was analyzed for somatic point mutaions, using the RNA-Seq data to determine mutation expression. This study contains the patient matched RNA-Sequencing data.

  Study EGAS00001003307

• MutWP5__CRUK_Mutographs_of_Cancer__Breast__BRCA_Carriers__Targeted_

  Sequencing of LCM-derived microbiopsies from 20 women who underwent risk-reducing reduction mastectomies due to germline BRCA1/2. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Targeted data will be used as a driver and clonality screen, highly clonal or driver-containing samples will subsequently be sent for whole-genome sequencing. Results from this portion of the study will be compared to women who had cosmetic breast reduction surgeries and those with cancer.

  Study EGAS00001003315

• RNA Editing in breast cancer

  High-throughput sequencing screens suggest that RNA editing, which consists in the substitution of adenosine with inosine by the RNA-specific adenosine deaminase (ADAR) enzyme, occurs at several thousand positions across the human genome. Recent evidences have shown that RNA-editing could promote proliferation and carcinogenesis; however, the general principles of ADAR activity on the transcriptome and how ADAR is controlled in cancers remain to be established. The main aim of this project was to investigate the phenomenon of RNA editing in breast and other cancers. The frequency of A-to-I editing was evaluated in 58 breast cancers equally distributed among the different molecular subtypes and 10 normal breast tissues. The analysis was focused on defining: the relationship between the global amount of editing and ADAR expression; the ability to predict the level of editability of specific sites; the distribution of editing in normal and tumour samples and among different breast cancer subtypes; and the clinical, pathological and genomic factors affecting editing.

  Study EGAS00001000495

• DNA from colon cancer samples and matched normal samples was hybridized on Human 660W-Quad SNP arrays and sequenced in Illumina HiScanSQ.

  DNA from colon cancer samples and matched normal samples was hybridized on Human 660W-Quad SNP arrays and sequenced in Illumina HiScanSQ. The objective of the study was to introduce methodology for the detection of genomic copy number alterations (CNAs) using high-throughput sequencing data. The samples in this study allow the comparison of the results from the seqCNA R package with those from other methods that detect copy number alterations (CNAs) in tumoural samples, either using SNP-array data or high-throughput sequencing data.

  Study EGAS00001000558

• Ewings_Sarcoma_RNA_seq_drug_sensitivity

  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.

  Study EGAS00001000419

• The subclonal architecture of metastatic breast cancer: Results from a prospective community-based rapid autopsy program 'CASCADE'

  Background: Understanding the cancer genome is seen as a key step in improving outcomes for cancer patients. Genomic assays are emerging as a possible avenue to personalised medicine in breast cancer. The majority of work in this area has targeted primary tumours however, and very few studies have performed comprehensive profiling of advanced disease. Evolution of the cancer genome during the natural history of breast cancer is largely unknown, as is the profile of disease at death. We sought to study in detail these aspects of advanced breast cancers that have resulted in lethal disease. Methods and Findings: Three patients with ER-positive, HER2-negative breast cancer and one patient with triple negative breast cancer underwent rapid autopsy as part of an institutional prospective community-based rapid autopsy program. Cases represented a range of management problems in breast cancer, including late relapse after early stage disease; de novo metastatic disease; discordant disease response and disease refractory to treatment. Between 5 and 12 metastatic sites were collected at autopsy together with available primary tumours and longitudinal metastatic biopsies taken during life. Samples underwent paired tumour-normal whole exome sequencing and single nucleotide polymorphism arrays. Subclonal architectures were inferred by jointly analysing all samples from each patient. Mutations were validated using high depth amplicon sequencing.Between cases, there were significant differences in mutational burden, driver mutations, mutational processes and copy number variation. Within each case, we found dramatic heterogeneity in subclonal structure from primary to metastatic disease and between metastatic sites, such that no single lesion captured the breadth of disease. Metastatic cross seeding was found in each case and treatment drove subclonal diversification. Subclones displayed parallel evolution of treatment resistance in some cases, and apparent augmentation of key oncogenic drivers as an alternative resistance mechanism. We also observed the key role of mutational processes in subclonal evolution.Limitations of this study include the potential for bias introduced by joint analysis of formalin fixed archival specimens with fresh specimens, and the difficulties in resolving subclones with whole exome sequencing. Other alterations that could define subclones such as structural variants or epigenetic modifications were not assessed. Conclusions: This study highlights the variety of mechanisms that shape the genome of metastatic breast cancer, and the value of studying advanced disease in detail. Treatment drives significant genomic heterogeneity in breast cancers which has implications for disease monitoring and treatment selection in the personalised medicine paradigm.

  Study EGAS00001002153

• Autozygosity_pilot___Pakistani_from_Birmingham

  The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry. In the UK there are large populations with very high first cousin marriage rates of 50-80%. Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations. This pilot study based on existing British-Pakistani cohort samples from Birmingham will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed. The data deposited in the EGA consist of low coverage whole exome sequencing on these samples.

  Study EGAS00001000511

• SCLC ctDNA sequencing

  In this study we have sequenced the ctDNA of 28 Small Cell Lung Cancer patients in the TP53 gene, each sample has been sequenced twice.

  Study EGAS00001003984

• Resistance to anti-EGFR therapy in colorectal cancer

  Monoclonal antibodies targeting the Epidermal Growth Factor Receptor (EGFR), such as cetuximab and panitumumab, have evolved to important therapeutic options in metastatic colorectal cancer (CRC). However, almost all patients with clinical response to anti-EGFR therapies show disease progression within a few months and little is known about mechanism and timing of resistance evolution. Here we performed whole genome sequencing of plasma DNA (plasma-Seq) from patients treated with anti-EGFR therapy. We demonstrate that development of resistance to anti-EGFR therapies is frequently associated with focal amplifications of KRAS, MET, and ERBB2. However, we also show that focal KRAS amplifications can be acquired in tumor genomes of patients under cytotoxic chemotherapy. Furthermore, we provide evidence that specific chromosomal polysomies, such as overrepresentations of 12p and 7p, harboring KRAS and EGFR, respectively, determine responsiveness to anti-EGFR therapy. In contrast, employing ultra-sensitive deep sequencing of genes associated with anti-EGFR resistance, such as KRAS, BRAF, PIK3CA, and EGFR, we did not observe the occurrence of novel, acquired mutations. Overall, whole-genome plasma DNA sequencing represents a non-invasive blood-based surrogate measure of changes in tumors. As such, plasma-Seq enables the identification of novel mutant clones and may therefore facilitate early adjustments of therapies that may delay or prevent disease progression.

  Study EGAS00001000582

• These are from Korean HCC samples with exome sequencing

  Hepatic resection is the most curative treatment option for early-stage hepatocellular carcinoma, but is associated with a high recurrence rate, which exceeds 50% at 5 years after surgery. Understanding the genetic basis of hepatocellular carcinoma at surgically curable stages may enable the identification of new molecular biomarkers that accurately identify patients in need of additional early therapeutic interventions. Whole exome sequencing and copy number analysis was performed on 231 hepatocellular carcinomas (72% with hepatitis B viral infection) that were classified as early-stage hepatocellular carcinomas, candidates for surgical resection. Recurrent mutations were validated by Sanger sequencing. Unsupervised genomic analyses identified an association between specific genetic aberrations and postoperative clinical outcomes. Recurrent somatic mutations were identified in 9 genes, including TP53, CTNNB1, AXIN1, RPS6KA3, and RB1. Recurrent homozygous deletions in FAM123A, RB1, and CDKN2A, and high-copy amplifications in MYC, RSPO2, CCND1, and FGF19 were detected. Pathway analyses of these genes revealed aberrations in the p53, Wnt, PIK3/Ras, cell cycle, and chromatin remodelling pathways. RB1 mutations were significantly associated with cancer-specific and recurrence-free survival after resection (p = 0.016 and p = 0.001, respectively). FGF19 amplifications, known to activate Wnt signalling, were mutually exclusive with CTNNB1 and AXIN1 mutations, and significantly associated with cirrhosis (p = 0.017). RB1 mutations can be used as a prognostic molecular biomarker for resectable hepatocellular carcinoma. Further study is required to investigate the potential role of FGF19 amplification in driving hepatocarcinogenesis in patients with liver cirrhosis and to investigate the potential of anti-FGF19 treatment in these patients.

  Study EGAS00001000604

• Childhood_Cancer_Paediatric_Behjati_SRF_WGS_Nanoseq_Managed_Access

  An exploratory study using WGS NanoSeq on a bait set of common paediatric cancer genes and cancer predisposition genes to assess mutations, mutational signatures, treatment effect, risk of relapse and to study the development of childhood cancer.

  Study EGAS00001007898

• MutWP5__CRUK_Mutographs_of_Cancer__Lung__PD37920__Targeted_

  Sequencing of LCM-derived microbiopsies from explanted lung from COPD patient. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Deep sampling throughout multiple regions of the lung will determine whether there are differences in smoking-related mutation burden in different portions of the lung. Targeted sequencing will be conducted on samples to identify drivers of interest and clonality of the samples, well-performing samples will be sent for subsequent whole-genome sequencing. Results from this portion of the study will be compared to other individuals with smoking-related diseases (COPD, pulmonary fibrosis, lung cancer), and normal, non-smoking lungs.

  Study EGAS00001003321

• MutWP5__CRUK_Mutographs_of_Cancer__Breast__Reduction_Mammoplasty__Exome_

  Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (<20 to >60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.

  Study EGAS00001003313

• Chromatin immunoprecipitation linked to next-generation whole genome sequencing (ChIP-Seq) for H3K36me3 in paediatric high grade glioma cell lines KKNS4 and SF188 with and without a G34V mutation in H3F3A

  Glioblastomas of children and young adults have a median survival of only 12-15months and are clinically and biologically distinct from histologically similar cancers in older adults1. They are defined by highly specific mutations in the gene encoding the histone H3.3 variant H3F3A2, occurring either at or close to key residues marked by methylation for regulation of transcription – K27 and G34. We performed chromatin immunoprecipitation linked to next-generation whole genome sequencing (ChIP-Seq) for H3K36me3 in order to test the hypothesis that, rather than total H3K36me3, the G34V mutation may instead result in differential binding of the trimethyl mark throughout the genome. Compared with H3F3A wild-type SF188 paediatric GBM cells, H3K36me3 was found to be significantly differentially bound in KNS42 cells at 5130 distinct regions of the genome corresponding to 156 genes. Concurrent whole genome DNA sequencing demonstrated that this was not confounded by copy number alterations. The cerebral hemispheric-specific G34 mutation drives a distinct expression signature through differential genomic binding of the K36 trimethylation mark (H3K36me3). The transcriptional program induced recapitulates that of the developing forebrain, and involves numerous markers of stem cell maintenance, cell fate decisions and self-renewal. Critically, H3F3A G34 mutations cause profound upregulation of MYCN, a potent oncogene which is causative of glioblastomas when expressed in the correct developmental context. This driving aberration is selectively targetable in this patient population by inhibiting kinases responsible for stabilisation of the protein.

  Study EGAS00001001437

• Targeted_sequencing_of_genes_recurrently_mutated_in_AML___part2

  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.

  Study EGAS00001000570

• PLCRC_study

  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.

  Study EGAS00001000612

• MutWP5__CRUK_Mutographs_of_Cancer__Lung__PD37920__WG_

  Sequencing of LCM-derived microbiopsies from explanted lung from COPD patient. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Deep sampling throughout multiple regions of the lung will determine whether there are differences in smoking-related mutation burden in different portions of the lung. Whole-genome sequencing will be conducted on samples identified as promising from the initial targeted data. Results from this portion of the study will be compared to other individuals with smoking-related diseases (COPD, pulmonary fibrosis, lung cancer), and normal, non-smoking lungs.

  Study EGAS00001003320

• Mutational context and diverse clonal development in early and late bladder cancer

  Bladder cancer shows multiple recurrences probably originating from a malignant field disease in the mucosa. Deep sequencing was used on a series of tumors to look into the clonal composition, mutational spectrum in non-aggressive tumors, and mutational context.

  Study EGAS00001000641

• Neoadjuvant chemotherapy alters the genomic landscape and immune microenvironment of breast cancers

  To characterize the effects of neoadjuvant chemotherapy (NAC) on the genome, transcriptome and tumor infiltrating leukocytes (TILs), we have conducted whole exome and whole transcriptome sequencing of a comprehensive, longitudinal breast cancer cohort consisting of 146 cases and 281 paired tumor samples. In total, 52 (38%) patients achieved pathologic complete response (pCR) while 85 patients (62%) had residual disease with standard chemotherapy regimen. Tumor biopsies were collected for each patient at three time points – pre-treatment, three weeks after the first cycle of anthracycline and cyclophosphamide (AC) and at the time of surgery after 3 more cycles of AC followed by 4 cycles of taxane or taxane plus Herceptin in case of HER2+ subtype.

  Study EGAS00001003354

• MutWP5__CRUK_Mutographs_of_Cancer__Lung__PD38233__WG_

  Sequencing of LCM-derived microbiopsies from explanted lung from COPD patient. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Deep sampling throughout multiple regions of the lung will determine whether there are differences in smoking-related mutation burden in different portions of the lung. Whole-genome sequencing will be conducted on samples identified as promising from the initial targeted data. Results from this portion of the study will be compared to other individuals with smoking-related diseases (COPD, pulmonary fibrosis, lung cancer), and normal, non-smoking lungs.

  Study EGAS00001003322

• MutWP5__CRUK_Mutographs_of_Cancer__Lung__PD38234__Targeted_

  Sequencing of LCM-derived microbiopsies from explanted lung from pulmonary fibrosis patient. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Deep sampling throughout multiple regions of the lung will determine whether there are differences in smoking-related mutation burden in different portions of the lung. Targeted sequencing will be conducted on samples to identify drivers of interest and clonality of the samples, well-performing samples will be sent for subsequent whole-genome sequencing. Results from this portion of the study will be compared to other individuals with smoking-related diseases (COPD, pulmonary fibrosis, lung cancer), and normal, non-smoking lungs.

  Study EGAS00001003325

• HKU Gastric Cancer Genomics study - WGS, DNA genotyping array, expression and methylation profiling

  HKU Gastric Cancer Genomics study - Whole Genome Sequencing, DNA genotyping array, Expression profiling and Methylation profiling

  Study EGAS00001000597

• Exome sequencing of a novel cervical cancer cell line

  Human cancer cell lines are largely used in the searching for new antineoplastic agents. However, due to the artifacts of a long-term in culture, cell lines do not always represent the realistic tumor cell behavior. This has motivated the development of models that better mimetics the tumor tissue, among them, the establishment of primary cell cultures. In this work, we establish and characterized a low-passage cervix cancer cell line from a Brazilian patient with squamous cell carcinoma. The phenotype confirms the epithelial and tumor origin, through cytokeratins, EpCAM, and p16 staining. Whole exome sequencing showed relevant somatic mutations in several genes including BRCA2, TGFBR1, and IRX2 genes. CNV analysis by nanostring and WGS revealed amplification in genes related mainly with kinases proteins, involved in proliferation, migration and cell differentiation, such as EGFR, PIK3CA, and MAPK7. Overexpression of EGFR was confirmed by phospho RTK-array and western blot analysis. Furthermore, the cell was sensitivity to cisplatin, with IC50 13 times lower than SiHa cell line. In conclusion, this cervical cancer cell line presents molecular alterations that are an important tool for leading pre-clinical studies of new drugs that target one or more of the altered pathways.

  Study EGAS00001003343

• Korean Lung Cancer - 36 pair WES data

  This study includes 36 paired samples of Korean Lung Cancer paitients.36 Lung Cnacer samples are paired with each normal(Saliva derived for control) sequencing data.The results of this WES study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.

  Study EGAS00001002843