8432 results for "canc*"

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• Exome array analysis of adverse reactions to fluoropyrimidine-based therapy for gastrointestinal cancer

  Fluoropyrimidines, including 5-fluororacil (5FU) and its pro-drug Capecitabine, are the common treatment for colorectal, breast, neck and head cancers – either as monotherapy or in combination therapy. Adverse reactions (ADRs) to the treatment are common and often result in treatment discontinuation or dose reduction. Factors contributing to ADRs, including genetic variation, are poorly characterized. We performed exome array analysis to identify genetic variants that contribute to adverse reactions.Our final dataset consisted of 504 European ancestry individuals undergoing fluoropyrimidine-based therapy for gastrointestinal cancer. A subset of 254 of these were treated with Capecitabine. All individuals were genotyped on the Illumina HumanExome Array.

  Study EGAS00001002763

• 560 whole-genome sequenced breast cancers

  A comprehensive characterisation and analysis of 560 human breast cancers through genome-wide approaches including genomics, transcriptomics and epigenomics.

  Study EGAS00001001178

• Multisample genomic analysis of solid childhood cancers using high resolution SNP-arrays, Whole Exome Sequencing and Targeted Deep Sequencing.

  We mapped the prevalence of genetically distinct clones over 248 regions in 54 childhood cancers. This revealed that primary tumors can simultaneously follow up to four evolutionary patterns in different anatomic areas. The most common pattern consists of a fluctuating presence over anatomic space of subclones with very few mutations. The second most common is a surprisingly stable coexistence, over vast areas, of clones with different changes in chromosome numbers. This is contrasted by a third, less frequent, pattern where a novel clone harboring driver mutations or structural chromosome rearrangements completely replaces its progenitor. The fourth and rarest pattern is the local emergence of a myriad of clones with TP53 inactivation. Strikingly, death from disease was limited to tumors exhibiting the two latter, most dynamic patterns.

  Study EGAS00001002662

• Paediatric_CNS_tumour_autopsy_DNA

  Investigation of early embryonic mutations can reveal the earliest stages of normal tissue development and the origins of paediatric cancers. Through widespread sampling of tumour, adjacent normal and distant normal samples at autopsy and whole genome sequencing, we aim to establish the point at which lethal paediatic brain tumours diverge from normal development. With many such tumours associated with germline predisposition mutations, we will also be able to investigate the tissue-specific effects these mutations induce.

  Study EGAS00001004771

• Identification_of_synthetic_lethal_genes_by_CRISPR_Cas9_library

  Sequencing is performed on PCR products from the amplification of gRNA segments introduced into cell lines (some are commercial, some are derived by collaborators, as described in HMDMC 13/076). Cellular DNA or RNA are not sequenced. This data is defined as "Other Biological/Biochemical Assay Data" under the WTSI datasharing guidelines and consequently will be released at the time of publication and/or through faculty websites. SEQUENCING DETAILS: in October 2016 3 DNA samples will be submitted for PCR amplification and purification through CGP pipeline using Thompson's custom primer set and PCR settings and sequencing with Hiseq using a custom protocol (with 3 forward reads to read sgRNA1, sgRNA2 and the index, optimized with Illumina Bespoke Sanger team); read length 50bp. The following set of samples will be submitted in later 2016 and ealry 2017 as cell pellet to be processed through CGP Cas9 pipeline (Thompson's oligos and protocols) and sequences on Hiseq (same custom sequencing protocol described above) We are utilizing a custom CRISPR/Cas9 library to identify synthetic lethal gene pairs. Cells will be transduced with LV expressing Cas9, then infected with LV expressign the library of 42'000 sgRNA pairs. Cell pellet will be collected from the cell population at different timepoints. The samples will be processed by CGP pipeline customized for the specific protocol and then sequenced to identify the 19bp of the sgRNA and quantify their representation.

  Study EGAS00001002117

• RNA_sequencing

  All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale. NB bam files for manuscript A_Proteomic_Chronology_of_Gene_Expression_through_the_Cell_Cycle_in_Human_Myeloid_Leukemia_Cells are now available at the following link:http://www.ebi.ac.uk/ena/data/view/ERP008483

  Study EGAS00001000310

• Genentech Small Cell Lung Cancer (SCLC) Screen

  Exome capture, RNA-Seq, whole genome sequencing of set of Small Cell Lung Cancer samples.

  Study EGAS00001000334

• Onco-exaptation of an Endogenous Retroviral LTR Drives IRF5 Expression in Hodgkin Lymphoma

  The transcription factor interferon regulatory factor 5 (IRF5) is upregulated in Hodgkin lymphoma (HL) and a key regulator of the aberrant transcriptome characteristic of this disease. Here we show that IRF5 upregulation in HL is driven by transcriptional activation of a normally dormant endogenous retroviral LOR1a long terminal repeat (LTR) upstream of IRF5. Specifically, through screening of RNA-seq libraries, we detected LTR-IRF5 chimeric transcripts in multiple HL cell lines but not in normal B-cell controls. In HL, the LTR was in an open and hypomethylated epigenetic state and we further show the LTR is the site of transcriptional initiation. Among HL cell lines, usage of the LTR promoter strongly correlates with overall levels of IRF5 mRNA and protein, indicating that LTR transcriptional awakening is a major contributor to IRF5 upregulation in HL. Taken together, oncogenic IRF5 overexpression in HL is the result of a specific LTR transcriptional activation. We propose that such LTR derepression is a distinct mechanism of oncogene activation (“onco-exaptation”) and that such a mechanism warrants further investigation in molecular and cancer research.

  Study EGAS00001001205

• Screening_for_human_epigenetic_variation_at_CpG_islands

  Many human characteristics, including susceptibility to disease, are determined genetically. An unexplored alternative to such genetic determination concerns epigenetic mechanisms such as DNA methylation. CpG islands (CGIs) are generally constitutively hypomethylated, however there are circumstances in which they become heavily methylated and, when coincident with a gene promoter, this invariably causes transcriptional silencing. CGI methylation occurs in normal tissues during processes such as X-inactivation, but abnormal patterns of methylation have also been implicated in disease. The vast majority of evidence relates to cancer, where silencing of multiple genes in this way appears to be a causal contributor to the cancer state. To address the role and extent of CGI methylation in ‘normal’ and diseased cells we applied MBD-affinity purification in conjunction with next generation sequencing in a panel of human brain autopsy samples. These samples represent a panel of individuals as well as specific brain regions and neurological pathologies.

  Study EGAS00001000074

• Human_Colorectal_Cancer_Exome_Sequencing

  In this experiment we sequenced a collection of genes identified as being mutated in a Sleeping Beauty Screen in a mouse colorectal Cancer Model in human tumours collected from patients with germline mutations in APC and also other familial CRC predisposition syndromes. We also sequenced the germline of these patients allowing us to identify somatically mutated genes. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001000077