7363 results for "canc*"

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• Chordoma_Sequencing_Project_Whole_Genome

  This is a continuation of the Chordoma Sequencing Project, prelim #G0175-122-CF. All cancers arise due to somatically acquired abnormalities in DNA sequence. Systematic sequencing of cancer genomes allows acquisition of complete catalogues of all classes of somatic mutation present in cancer. These mutation catalogues will allow identification of the somatically mutated cancer genes that are operative and characterise patterns of somatic mutation that may reflect previous exogenous and endogenous mutagenic exposures. In this application, we aim to perform whole genome sequencing on 10 chordoma matched genome pairs. The Chordoma Foundation will fund the RNA Sequencing/Methylation and SNP6 costs for this project while the whole genome and library sequencing will be covered under the CGP, 2012-2013 core WTSI internal funding. An additional sequencing of three cancer cell lines will be added to this work, financed by the Chordoma Foundation. In this project, the Chordoma foundation will pay for the additional costs of methylation, RNA Seq,

  Study EGAS00001000409

• Breast_Cancer_FRT_RNA_seq

  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.

  Study EGAS00001000420

• Y_chromosome_mis_segregation_in_the_DLD_1_cell_line

  Study of the well-established DLD-1 colorectal cancer cell line, engineered with an inactivatable Y centromere that leads to mis-segregation. The goal is to gain insights into the mechanism of chromothripsis due to chromosome mis-segration.

  Study EGAS00001002551

• Single_Cell_Targeted_Sequence_Capture

  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.

  Study EGAS00001000435

• B Cell Receptor Study From Metastatic Breast Cancer Tumour Samples

  B and T cells are key components of the adaptive immune system and play an important role in anti-cancer immunity. In this study, we performed an integrative analysis of the B cell and T cell repertoires across 27 metastatic breast tumours obtained from 8 donors with therapy-resistant lethal metastatic breast cancer at the time of a warm autopsy.

  Study EGAS00001006976

• Whole genome and transcriptome analysis of a sporadic and recurring parathyroid carcinoma

  Parathyroid carcinoma is an extremely rare endocrine malignancy with an estimated incidence of less than 1 per million population. Excessive secretion of parathyroid hormone, extremely high serum calcium level and the deleterious effects of hypercalcemia are the clinical manifestations of the disease. Up to 60% of patients develop multiple disease recurrences and although long-term survival is possible with palliative surgery, permanent remission is rarely achieved. Molecular drivers of sporadic parathyroid carcinoma have remained largely unknown. Previous studies, mostly based on familial cases of the disease, suggested a potential role for the tumor suppressor MEN1 and proto-oncogene RET in benign parathyroid tumorigenesis while the tumor suppressor HRPT2 and proto-oncogene CCND1 may also act as drivers in parathyroid cancer. Here, we report the complete genomic analysis of a sporadic and recurring parathyroid carcinoma. Mutational landscapes of the primary and recurrent tumor specimens were analyzed using high throughput sequencing technologies. Such molecular profiling allowed for identification of somatic mutations never previously identified in this malignancy. These included single nucleotide point mutations in well characterized cancer genes such as mTOR, MLL2, CDKN2C and PIK3CA. Comparison of acquired mutations in patient-matched primary and recurrent tumors revealed loss of PIK3CA activating mutation during the evolution of the tumor from the primary to the recurrence. Structural variations leading to gene fusions and regions of copy loss and gain were identified at a single-base resolution. Loss of short arm of chromosome 1 along with somatic mis-sense and truncating mutations in CDKN2C and THRAP3, respectively, provide new evidence for the potential role of these genes as tumor suppressors in parathyroid cancer. The key somatic mutations indentified in this study can serve as novel diagnostic markers as well as therapeutic targets.

  Study EGAS00001000484

• ERG ALTERATIONS DEFINE A NOVEL SUBTYPE OF ACUTE LYMPHOBLASTIC LEUKEMIA

  Structural chromosomal alterations are a hallmark of acute lymphoblastic leukemia (ALL) yet many patients lack an identifiable abnormality on conventional cytogenetic analysis. Here, using integrated analysis of genome-wide DNA copy number and gene expression data of 1764 childhood and adult ALL cases, including whole-genome, exome and mRNA-sequencing of 72 cases, we report a novel subtype of B-progenitor ALL (B-ALL) representing 4-13% of B-ALL cases characterized by a distinct gene expression profile, and focal deletions of ERG (ETS related gene) in 56% of cases. These cases are characterized by expression of a ERG transcript that utilizes a novel exon in intron 6 of ERG spliced to the canonical reading frame of ERG exons 7-10, encoding a 27 kDa C-terminal ERG protein that retains the ETS and transactivating domains but lacks the N-terminal pointed and regulatory domains. This protein is a competitive inhibitor of wild-type ERG and is leukemogenic in vivo. ERG-altered ALL cases have a favourable outcome despite the presence of alterations associated with poor prognosis in non-ERG ALL, such as deletions of IKZF1. These findings identify a new subtype of leukemia characterized by a novel mechanism of ETS transcription factor dysregulation in cancer.

  Study EGAS00001000514

• HSC_population_dynamics___LEUK4_samples

  My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology. The four major questions I will address are: 1. How do age and aging affect normal human HSC dynamics in vivo? 2. How do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics? 3. Is response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood? 4. How are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?

  Study EGAS00001004247

• Analysis of DNA methylation in normal B cells and chronic lymphocytic leukemia

  Charting differences between tumors and normal tissue is a mainstay of cancer research. However, clonal tumor expansion from complex normal tissue architectures potentially obscures cancer-specific events, including divergent epigenetic patterns. Using whole-genome bisulfite sequencing of normal B cell subsets, we observed broad epigenetic programming of selective transcription factor binding sites coincident with the degree of B cell maturation. By comparing normal B cells to malignant B cells from 268 patients with chronic lymphocytic leukemia (CLL), we showed that tumors derive largely from a continuum of maturation states reflected in normal developmental stages. Epigenetic maturation in CLL was associated with an indolent gene expression pattern and increasingly favorable clinical outcomes.As second study using these samples focued on evolution and resulting intra-tumor heterogeneity in CLL. We used 450k bead-chip arrays to study DNA methylomes in 68 chronic lymphocytic leukemia (CLL) cases, including 28 serial cases. The result establishs linked evolution of epigenetic and genetic alterations in progressive disease, revealing an important aspect of the biology of epigenetics in cancer.

  Study EGAS00001000534

• CPC-GENE Prostate Cancer Heterogeneity Study

  Herein we describe a molecular portrait of potentially curable, Gleason 7 and intermediate risk prostate cancer based on genome-wide CNV profiles of 96 patients, and subsequent whole-genome sequencing of 28 tumours from 10 patients, using DNA quantities that are achievable in diagnostic biopsies (50 ng). We show that Gleason 7 cancer is highly heterogeneous at the SNV, CNV, and intra-chromosomal translocation levels, and is characterized by a very low number of recurrent SNVs but significant structural variation. We identified a novel recurrent MYCL1 amplification, which was strongly associated with TP53 deletion and prognostic for biochemical recurrence in this cohort. Moreover, we identified clear evidence of divergent tumour evolution in multi focal cancer and, in 2/5 cases evaluated, multiple tumours of independent clonal origin. Taken together, these data represent the first systematic evaluation of the differential genomics of potentially curable prostate cancer, and strongly suggest that a more robust understanding of the relationship between genetic heterogeneity and clinical outcomes is required to effectively develop biomarkers of prognosis based on tumour genomics.

  Study EGAS00001000549