3288 results for "ovarian cancer"

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• Comprehensive genetic landscape, immune checkpoint profiling, and establishment of patient-derived xenograft (PDX) of metachronous brain tumors from constitutive mismatch repair deficiency with a biallelic variant on MSH6

  Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare genetic disorder caused by biallelic pathogenic variants in mismatch repair genes (PMS2, MSH6, MLH1, or MSH2) resulting in the development of a variety of different tumors, including brain neoplasms. This study molecularly characterized a Brazilian child with CMMRD, harboring two metachronous brain tumors (medulloblastoma and high-grade glioma), and established a patient-derived xenograft (PDX) of the CMMRD-associated brain tumor. Keywords: Brazil, Constitutional mismatch repair deficiency syndrome, exome, MSH6, medulloblastoma, high-grade glioma.

  Study EGAS50000000351

• The_Causes_of_Clonal_Blood_Cell_Disorders_Study___SCOR

  We will take a bone marrow aspirate and peripheral blood samples from a healthy patient aged around 60, and use flow cytometry to isolate 100 HSCs, 50 MEPs, and 50 GMPs. We will grow these up into colonies, then whole genome sequence each colony. Somatic mutations will act as a unique barcode for each clone. We will then design a panel for targeted resequencing of the mutations that we find. It will then be possible to look for these mutations in the peripheral blood over several years, to see the dynamics of how HSCs contribute to the peripheral blood in health.

  Study EGAS00001002132

• WXS of 147 lung cancer patients treated with immunotherapy

  We first attempted to predict MHC-binding neoantigens at high accuracy with convolutional neural networks. This prediction model outperformed previous methods in > 70% of test cases. Importantly, our method remarkably increased the predictive value of neoantigen load especially in combination with known resistance parameters. We then developed a classifier that can predict resistance from point mutations that are deleterious to protein function. Notably, genes involved in the adaptive immune response, cytokine signaling,and EGFR signaling held high explanatory power. Furthermore, when integrated with our neoantigen profiling, these anti-immunogenic mutations revealed significantly higher predictive power than known resistance factors.

  Study EGAS00001003781

• Characterization of four subtypes in morphologically normal tissue excised proximal and distal to breast cancer

  Our study provides insight into molecular alterations in HN tissues within the affected breast and offers a greater understanding of the spatial implications of these aberrations. This was achieved by performing a comprehensive analysis of RNA sequencing data and proteomic profiles from breast cancers (n=19) and their matched HN tissues (n=38), healthy breast from cosmetic reduction mammoplasty (RM; n=5), and risk reducing mastectomies (RR, n=5), with peritumoral samples excised at proximal (TP, <2 cm) and distal (TD, 5-10 cm) sites from the primary tumor.

  Study EGAS00001004510

• Unraveling metastatic progression of breast cancer

  To reconstruct the trajectories of BC progression, we performed exome sequencing (Illumina HiSeq2000, Truseq DNA sample preparation kit v2 and Exome Enrichment Kit v2; alignement done with BWA, substitutions and indels called with GATK and DINDEL respectively) coupled to validation by Sequenom and deep re-sequencing (ongoing), as well as copy number (CN) analyses (Oncoscan, Affymetrix) on DNA from matched primary (n=1-6/pt), axillary lymph node (ALN, n=1-6 for 4 pts), local recurrence (for 1 pt) and distant metastatic (n=1-5/pt) FFPE samples obtained from an autopsy series of 10 BC pts.

  Study EGAS00001000760

• NRG1 Fusions in KRAS Wild-type Pancreatic Cancer (H021)

  We used whole-genome and transcriptome sequencing to identify clinically actionable gene fusions in young adults with KRAS wild-type (KRASwt) pancreatic ductal adenocarcinoma (PDAC). These alterations included recurrent NRG1 rearrangements predicted to drive PDAC development through aberrant ERBB receptor-mediated signaling, and pharmacologic ERBB inhibition resulted in clinical improvement and remission of liver metastases in two patients with NRG1-rearranged tumors that had proved resistant to standard treatment. Our findings demonstrate that systematic screening of KRASwt tumors for oncogenic fusion genes will substantially improve the therapeutic prospects for a sizeable fraction of PDAC patients.

  Study EGAS00001002759

• NanoSring of PBMC from bladder cancer and RCC patients

  PBMCs from patients were isolated using 50 mL Leucosep™ tubes (Greiner Bio-One International, Germany) and Ficoll-Paque™ PLUS (GE Healthcare, Sweden). Whole blood drawn into sodium heparin blood collection tubes were diluted 3x with phosphate-buffered saline (PBS) without calcium or magnesium (Lonza, Walkersville, MD). Diluted cell suspensions were carefully layered on Leucosep tubes and centrifuged for 15 minutes at 800 x g at room temperature (RT). Interphase containing PBMCs were harvested and washed with PBS and subsequently centrifuged for 10 minutes at 250 x g at RT before further processing.

  Study EGAS00001004229

• Exploring_the_heterogeneity_of_sarcoma_using_single_cell_sequencing_

  Multi region samples are collected from patients, with consent, immediately after resection of the tumour. Samples are digested and sorted using FACS as single cells into lysis buffer. Cells are then stored until further processing for G&T-seq. After sequencing, we will explore intra-tumour heterogeneity using computational approaches to integrate RNA and DNA data onto the tumour phylogeny 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 EGAS00001002866

• Panbody_nanoseq

  Different cell types within the human body are subject to different endogenous and exogenous exposures which may result in distinct patterns of mutagenesis. In non-clonal tissues, it is difficult to assess these mutational patterns, including the rate at which they occur. This study will examine the mutational rates and signatures operating across a wide range of normal tissues using the nanoseq technology to reliably call variants, irrespective of their clonal composition. Each cell type will be enriched for using laser capture microdissection. This will serve as a reference against which future work on benign and malignant disease entities can be compared.

  Study EGAS00001005521

• Genomic Profiling Reveals Spatial Intra-tumour Heterogeneity in Follicular Lymphoma

  Follicular lymphoma (FL) is an incurable indolent non-Hodgkin’s lymphoma (NHL) that behaves heterogeneously and is synonymous with the reciprocal translocation t(14;18)(q32;q21), leading to aberrant constitutive over-expression of BCL2 [ref]. High risk groups with poor overall survival include patients that transform to a high grade lymphoma, most commonly diffuse large B cell lymphoma (DLBCL) or progress early (within 2 years) of receiving treatment. Recently several studies have shed light on the diverse genomic landscape of FL, with frequently mutated genes including those involved in chromatin remodelling, (CREBBP, KMT2D, EZH2, EP300), immune modulation (TNFRSF14), JAK-STAT (STAT6, SOCS1), NF-ĸB (CARD11, MYD88, TNFAIP3) and mTORC1 signalling (RRAGC) [ref]. To date, the majority of these studies have either focussed on inter-patient genetic heterogeneity or established the extent of clonal heterogeneity as a patient’s tumour evolves over time. Furthermore, these temporal studies have alluded to the existence of a tumour-repopulating population (referred to as the common progenitor cell (CPC)) that evades treatment and acts as a reservoir, seeding each subsequent relapse and transformation event. Although these previous studies have illuminated the longitudinal clonal dynamics that occur in FL, our understanding of the degree of spatial or intra-tumour heterogeneity (ITH) that exists within an individual patient thus far remains limited. Earlier studies have predominantly focused on differences in cytological grade and immunophenotype between spatially separated lymph nodes and bone marrow, the most common site of extra-nodal involvement in FL, with genomic profiling restricted to examining somatic hypermutation patterns in IgVH genes [ref]. In contrast next generation sequencing has been increasingly utilised in solid organ malignancies to derive comprehensive genomic profiles from spatially separated sites. The seminal study by Gerlinger et al revealed profound differences in the genetic make-up between individual primary and metastatic sites of renal cell carcinoma [ref]. Significant heterogeneity has since been demonstrated both between and within lesions in the same patient in lung, pancreas and breast cancer with presumed driver mutations distributed within the “branches” of the evolutionary phylogenetic tree, suggesting that a single biopsy is incapable of capturing the full genomic heterogeneity of an individual’s malignancy [ref]. This geographical heterogeneity not only adds to the diverse pool of tumour subclones that may contribute to drug resistance mechanisms but importantly, presents a major obstacle for precision-based approaches focussed on targeting specific lesions within a single biopsy. In FL, the exponential increase in clinical trials using novel agents such as EZH2, PI3K and BTK inhibitors reflects this shift in cancer care and along with the development of molecular prognostic scores such as the m7-FLIPI highlights the clinical need to accurately define genomic alterations with clinical relevance. As the majority of FL patients manifest disseminated tumour involvement, we sought to uncover the extent and clinical importance of spatial heterogeneity in FL by comprehensively genetically profiling 22 synchronously removed spatially separated biopsies from 9 patients. Using a combination of whole exome and targeted deep sequencing, our results inferred the complex subclonal architecture within these tumours and the mutational differences between anatomical sites, demonstrating cases with significant intrinsic genetic diversity.

  Study EGAS00001002492