8432 results for "canc*"

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• SCAT_osteosarcoma_sequencing

  Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 50 osteosarcoma cancers and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 100 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes

  Study EGAS00001000196

• 1 Intratumoral genetic heterogeneity and clonal evolution following neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal tumors.

  Purpose: Neoadjuvant chemoradiotherapy (nCRT) is the standard treatment forpatients with locally advanced rectal cancer. However, little is known about the effect of nCRT in the mutational landscape and intratumoral genetic heterogeneity (ITGH) of rectal tumors. Moreover, response to nCRT vary substantially among patients and the genetic determinants of treatment response are not fully understood. Here, we sought to determine the impact of nCRT in the mutational landscape and ITGH of rectal tumors and to identify putative drivers of therapeutic resistance. Patients and Methods: We analyzed whole-exome sequencing (WES) and clinical data from 79 primary non-treated rectal cancers obtained from The Cancer Genome Atlas (TCGA). We also compared the mutational landscape of a matched set of peripheral blood cells, irradiated tumor-adjacent colonic mucosa and pre and post-treatment tumor samples to determine the iatrogenic effects of nCRT and its impact in tissue genetic heterogeneity. Finally, we performed WES of 7 matched pre and post-treatment tumor samples to examine how nCRT affects the clonal architecture of rectal tumors. Results: We show that rectal tumors exhibit remarkable ITGH, which increases with disease progression. We also show that nCRT, per se, does not introduce novel somatic mutations, nor alters the clonal architecture of the irradiated colonic mucosa. Instead, we show that it acts as a potent selective pressure, favoring the expansion of tumor cell subpopulations more prone to resist therapy and increasing ITGH in the residual tumor. Conclusion: Our results reveal the highly heterogeneous and dynamic clonal architecture of rectal tumors undergoing nCRT. Our results also uncover putative genetic determinants of response to nCRT and a possible role for ITGH in predicting treatment outcome.

  Study EGAS00001003250

• Evaluation_of_size_selection_on_cancer_specific_sequencing_libraries

  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.

  Study EGAS00001000293

• Robust detection of translocations in lymphoma FFPE samples using Targeted Locus Capture-based sequencing

  Chromosomal translocations with immunoglobin (IG) loci are the classic drivers in a large subset of B-cell lymphomas. Detection of these translocations is important for confirmation of diagnosis and for prognosis and therapy decisions. Currently, molecular diagnosis of translocations in lymphomas is not addressed well by Next Generation Sequencing (NGS). The standard method for detection of translocations is Fluorescence In Situ Hybridization (FISH), which is labor-intensive, and can be difficult to interpret. There is a need for a robust technology that can be standardized. Targeted Locus Capture (TLC) selectively enriches and sequences entire genes based on the crosslinking of physically proximal sequences, and thereby enables complete sequencing of genes of interest, including detection of large structural variants. Because the technology is based on the crosslinking and fragmenting of DNA, it has particular advantages in the analysis of Formalin-Fixed, Paraffin-Embedded (FFPE) samples, in which DNA is inherently crosslinked and fragmented. In order to validate the FFPE-TLC technology as a novel approach for translocation detection in lymphoma samples, we have developed a panel assay containing genes with frequent translocations (MYC, BCL2, BCL6, IG loci). With this assay we have analyzed >140 lymphoma and control FFPE samples of variable input amounts and qualities that had previously been analyzed with FISH, and a subset also with standard targeted NGS. Good concordance with FISH results was observed for both translocation positive and negative samples. In 10 cases for which FFPE-TLC detected a relevant fusion and FISH had been called negative, discordance could be explained by higher sensitivity of FFPE-TLC or by inconclusive FISH results. In a specific case, FFPE-TLC detected a small-distance rearrangement on chromosome 3 that caused a BCL6 fusion but led to insufficient and therefore undetectable break-apart with FISH. Secondly, the FFPE-TLC approach was tested on a set of 19 B-cell lymphoma FFPE samples that had previously been analyzed using standard targeted NGS and FISH and was enriched for discordant results between these methods. FFPE-TLC-based NGS enables more robust translocation calling as the detection relies on broad sequencing coverage across the translocation partner rather than on breakpoint sequences only. In 3 cases, FFPE-TLC could proof false negative calls in standard targeted NGS due to breakpoints located in regions difficult to capture or to sequence. In 1 case, standard targeted NGS had made a false positive call on a breakpoint sequence that was shown to be caused by a small insertion rather than a genuine translocation. This study shows that FFPE-TLC promises to be a robust alternative for FISH analysis and standard targeted NGS procedures in lymphoma diagnostics and possibly in other cancers with frequent structural variants. The FFPE-TLC approach enables a single, DNA-based NGS test detecting both small mutations and translocations.

  Study EGAS00001004760

• Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing

  Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing

  Study EGAS00001000566

• DERMATLAS__Hidradenoma_papilliferum_RNAseq

  Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis. Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles. The cases in this cohort are hidradenoma papilliferums.

  Study EGAS00001005715

• Canadian Prostate Cancer Genome Network

  Over 5 years, CPC-GENE will sequence the genomes of 350 intermediate risk prostate cancers to identify genetic signatures that differ in cancers that responded well to treatment compared with those that did not. CPC-GENE will also sequence multiple regions of prostate cancer from the same gland to determine if and how the genetic make-up of prostate cancer varies within an individual man’s prostate

  Study EGAS00001000900

• Targeted and shallow whole genome sequencing identifies therapeutic opportunities in p53abn endometrial cancers

  Purpose: Shallow whole genome sequencing (sWGS) can detect copy number (CN) aberrations. In high-grade serous ovarian (HGSOC) sWGS identified CN signatures such as homologous recombination deficiency (HRD) to direct therapy. We applied sWGS with targeted sequencing to p53abn endometrial cancers (ECs) to identify additional prognostic stratification and therapeutic opportunities. Experimental Design: sWGS and targeted panel sequencing was performed on formalin-fixed paraffin-embedded p53abn ECs. CN alterations, mutational data and CN signatures were derived, and associations to clinicopathologic and outcomes data were assessed. Results: In 187 p53abn ECs, 5 distinct CN signatures were identified. Signature 5 was associated with BRCA1/2 CN loss with features similar to HGSOC HRD signature. 22% potential HRD cases were identified, 35 patients with signature 5, and 8 patients with BRCA1/2 somatic mutations. Signatures 3 and 4 were associated with whole genome duplication, and CCNE1, ERBB2 and MYC amplifications, with mutations in PIK3CA enriched in signature 3. We observed improved overall survival (OS) for patients with signature 2 and worse OS for signatures 1 and 3. 28% of patients had CCNE1 amplification and this subset was enriched with carcinosarcoma histotype. 34% of patients, across all histotypes, had ERBB2 amplification and/or HER2 overexpression on immunohistochemistry, which was associated with worse outcomes. Mutations in PPP2R1A (29%) and FBXW7 (16%) were among the top 5 most common mutations. Conclusions: sWGS and targeted sequencing identified therapeutic opportunities in 75% of p53abn EC patients. Further research is needed to determine the efficacy of treatments targeting these identified pathways within p53abn ECs.

  Study EGAS00001007661

• Myeloproliferative_Neoplasms__MPN__Exome_Validation_Study

  Experiments using targeted pulldown methods will be sequenced to validate findings in the exomes of patients with Myeloproliferative Neoplasms (MPN).

  Study EGAS00001000404

• DERMATLAS__Porocarcinoma_WES

  Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis. Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles. The cases in this cohort are porocarcinomas.

  Study EGAS00001005720