7359 results for "canc*"

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• Complete Genomics paired end sequencing; Ovarian cancer

  We sequenced the genomes from a monozygotic twin discordant for schizophrenia and a tumor-normal pair of an ovarian cancer patient. Using whole-genome twin data to discriminate between correctly identified single nucleotide variants (SNVs) and errors a strategy for the accurate detection of SNVs was developed. By applying stringent sequencing quality measures, excluding error-prone regions and selecting SNVs identified by different mapping and variation calling algorithms, error rates were ~37-fold reduced. This enabled us to identify the first discordant SNVs in monozygotic twins using whole-genome sequencing. In addition, by showing that novel SNVs are highly enriched in errors, accurate estimates of the number of novel and rare SNVs occurring in unrelated Caucasian individuals were obtained. Finally, somatic mutations in coding and regulatory sequences were reliably identified in the highly rearranged ovarian tumor. Overall, our data demonstrate that strategies to reduce error rates in whole-genomes are required for disease gene discovery.

  Study EGAS00001000158

• PanCuRx Translational Research Initiative

  The goal of the PanCuRx TRI is to seek solutions to the high fatality rate of pancreatic adenocarcinoma (PDAC), the most common type of pancreatic cancer, by generating new knowledge about the genetics and biology of the disease, mechanisms of how tumours grow and tailored treatment options. PDAC is the fourth leading cause of cancer death in Canada and is expected to become the second-leading cause of cancer death within the next decade. The current five-year survival rate of eight per cent is the lowest of all epithelial cancers. There are major clinical challenges to treating the disease, including the fact that PDAC spreads to other parts of the body early so surgical removal of the tumour benefits few patients, that PDAC has proven relatively resistant to systemic therapies such as chemotherapy and that there has been limited benefit from the use of newer molecular targeted agents. The PanCuRx team has created the world’s first resource of tumour-purified PDAC whole genomes; more than 500 PDAC samples, with combined clinical annotation, have been successfully sequenced and analyzed at the Ontario Institute for Cancer research in Toronto. The resulting clinical genomic resource created from this data has led to multiple new findings that have established a framework to better understand PDAC biology and lays the foundation for new genomic approaches to better understanding the disease. The team also launched a clinical trial called COMPASS (Comprehensive Molecular Characterization of Advanced Ductal Pancreas Adenocarcinoma for Better Treatment Selection: A Prospective Study), which is recruiting patients with advanced PDAC (both locally advanced and metastatic) at The Princess Margaret Cancer Centre (PM) in Toronto. The study uses the molecular results from individual patient tumours to guide selection of better second line treatment on a case-by-case basis. The primary objective of the initial study was to assess the feasibility of collecting tumour materials from patients with advanced PDAC and delivering results within 56 days of biopsy. Having achieved this objective, the trial has expanded to other cancer centres across Canada. Pancreatic cancer is one of the most deadly forms of cancer and outcomes have not improved in four decades. The PanCuRx initiative is providing a better understanding of the disease and actively applying new knowledge to cancer patients through clinical trials. This knowledge will help to improve quality of life and prolong survival for pancreatic cancer patients worldwide.

  Study EGAS00001002543

• Osteosarcoma_Exome_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 EGAS00001000163

• Exome_sequencing_of_blastic_plasmacytoid_dendritic_cell_neoplasms

  Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive haematological malignancy derived from precursors of plasmacytoid dendritic cells. Due to the rarity of BPDCNs our knowledge of their molecular pathogenesis was until recently confined to observations describing reccurent chromosomal deletions involving chromosomes 5q, 12p, 13q, 6q, 15q and 9. A recent publication went on to delineate the common deleted regions using aCGH and demonstrated that these centred around known tumour suppressor genes including CDKN2A/B (9p21.3), RB1 (12p13.2-14.3), CDKN1B (13q11-q12) and IKZF1 (7p12.2).These mutations are found recurrently in several different cancers and in most cases are thought to be involved in tumour progression rather than initiation. However, the well-defined nature and cellular ontogeny of these neoplasms suggests strongly that they share one or a few characteristic mutations as has been demonstrated for other uncommon but well-defined neoplasms such as Hairy Cell Leukemia (BRAF) and ovarian Granulosa Cell tumours (FOXL2).

  Study EGAS00001000171

• BRAF_and_MEK_resistant_cell_line_clones

  The Sanger Institute has the largest collection of genetically-characterised cancer cell lines world-wide (we have collected >1000 human cancer cell lines which are being screened against >400 cancer therapeutics (http://www.sanger.ac.uk/genetics/CGP/translation). These lines have been characterized to the level of gene copy number, gene expression and cancer gene mutation sequence data. This has enabled us to select melanoma lines with varying BRAF mutational status and that show sensitivity to a range of BRAF inhibitors. Sensitive lines are being used to generate resistant clones by serial exposure to increasing concentrations of BRAF and MEK inhibitors and these are being characterised by genome-wide copy number analysis as well as by whole exome sequencing.

  Study EGAS00001000172

• Lung_Multi_site_Targeted_Sequence_Capture

  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.

  Study EGAS00001000436

• Direct Detection of Early-stage Cancers Using Circulating Tumor DNA

  Early detection and intervention are likely to be the most effective means for reducing morbidity and mortality of human cancer. However, development of methods for noninvasive detection of early-stage tumors has remained a challenge. We have developed an approach called targeted error correction sequencing (TEC-Seq) that allows ultrasensitive direct evaluation of sequence changes in circulating cell-free DNA using massively parallel sequencing. We have used this approach to examine 58 cancer-related genes encompassing 81 kb. Analysis of plasma from 44 healthy individuals identified genomic changes related to clonal hematopoiesis in 16% of asymptomatic individuals but no alterations in driver genes related to solid cancers. Evaluation of 200 patients with colorectal, breast, lung, or ovarian cancer detected somatic mutations in the plasma of 71, 59, 59, and 68%, respectively, of patients with stage I or II disease. Analyses of mutations in the circulation revealed high concordance with alterations in the tumors of these patients. In patients with resectable colorectal cancers, higher amounts of preoperative circulating tumor DNA were associated with disease recurrence and decreased overall survival. These analyses provide a broadly applicable approach for noninvasive detection of early-stage tumors that may be useful for screening and management of patients with cancer.

  Study EGAS00001002577

• Exome-wide somatic mutation characterization of small bowel adenocarcinoma

  Small intestinal adenocarcinoma (SIA) is a rare and aggressive form of cancer with limited treatment options. To further characterize the somatic mutation landscape of this tumor type, exome sequencing was conducted on a population-based set of SIA samples from all three parts of the small intestine. Archival tissue from 106 tumors with comprehensive clinical patient information entered exome sequencing from a patient series consisting of SIA cases diagnosed in Finland between the years 2003-2011. Paired-end exome sequencing was performed using Illumina HiSeq 4000, and OncodriveFML was used to identify significantly mutated genes from the exome data. Also mutational signature and pathway enrichment analyses were performed.

  Study EGAS00001002559

• Somatic_mutation_and_clonal_evolution_in_the_human_bladder_WES

  In this study, we aim to characterise the landscape of mutation and clonal selection in the human bladder. The data in this study will be generated by whole-exome sequencing of laser-dissected microbiopsies from the bladder. The samples utilised in this study will include urothelium from transplant donors with no history of bladder cancer and cystectomy specimens from patients with bladder cancer.

  Study EGAS00001002842

• Meningioma_Exome

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

  Study EGAS00001000177