9295 results for "cancer rna-seq"

in 30.44 milliseconds.

• Somatic_mutation_in_skin_epidermis__SMS_

  We aim to assess the range and depth of mutations in genes linked with cancer in skin epidermis surrounding lesions which are undergoing surgical removal. Patient history will be collected to provide a detailed outline of tumour type (including histology), skin type, and sunlight exposure. We will perform ultra-deep targeted sequencing using genes implicated in cancer to try and understand the background of mutations surrounding these lesions

  Study EGAS00001002165

• Somatic_mutation_and_clonal_evolution_in_the_human_bladder_Novaseq

  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-genome 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 EGAS00001003433

• Phylogenetic analysis of combined lobular and ductal carcinoma of the breast

  Breast cancer manifests in diverse forms, with particular reference to various cell types harboring different mutations and gene expression profiles. To elucidate the clonal relationship between cancer cells in tumors composed of both ductal and lobular phenotypes, we analyzed two combined lobular and ductal carcinoma (CLDC) cases, including one mixed ductal-lobular carcinoma (MDL) lesion, by next generation sequencing.

  Study JGAS000300

• Platelet RNAseq data for SLFN14 K219N patients

  Pathogenic missense variants in SLFN14, which encodes an RNA endoribonuclease protein that regulates rRNA degradation, are known to cause inherited thrombocytopenia with impaired platelet aggregation and ATP secretion. Despite rather mild laboratory defects, these patients display an obvious bleeding phenotype. The function of SLFN14 in megakaryocyte (MK) and platelet biology is unknown. This study aims to characterize the platelet transcriptome in patients with a SLFN14 K219N variant and model the disease in the immortalized megakaryocyte cell line imMKCL. Total platelet RNA was sequenced for two patients and 19 healthy controls. Differential gene expression analysis yielded a total of 2999 and 2888 significantly (|log2FC|>1, FDR<0.05) up- and downregulated genes, respectively. Remarkably, these downregulated genes were not enriched for any biological pathway while upregulated genes were enriched for pathways involved in (mitochondrial) translation and transcription with a significant upregulation of 134 ribosomal protein genes (RPG). Heterozygous and homozygous SLFN14 K219N imMKCL showed a defect in MK differentiation that aggravated during cell passaging of undifferentiated cells and in proplatelet formation. SLFN14 defective platelets and MK showed signs of rRNA degradation while this was absent in undifferentiated imMKCL cells. Upregulation of RPG through increased mTOR signaling in SLFN14 K219N MK seems to be a compensatory response for rRNA degradation. Indeed, mTOR inhibition with rapamycin resulted in further enhanced rRNA degradation in SLFN14 K219N MK. Taken together, our study indicates dysregulation of mTOR-regulated ribosomal biogenesis as the disease mechanism for SLFN14-related thrombocytopenia.

  Study EGAS00001006339

• Center for Sub-Cellular Genomics

  A cell is a highly complex system with distributed molecular physiologies in structured sub-cellular compartments whose interplay with the nuclear genome determine the functional characteristics of the cell. A classic example of distributed genomic processes is found in neurons. Learning and memory require modulation of individual synapses through RNA localization, localized translation, and localized metabolites, such as those from dendritic mitochondria. Dendrites of neurons integrate distributed synaptic signals into both electrical and nuclear transcriptional response. Dysfunction of these distributed genomic functions in neurons can result in a broad spectrum of neuropsychiatric diseases such as bipolar and depressive disorders, autism, among others. The Center for Sub-Cellular Genomics' (CSG) mission is to develop new technologies to enable the dissection of complex genomic interactions within a single cell. New technologies include methods to target DNA and RNA sampling at sub-cellular resolution in live cells; high-throughput isolation and microfluidics chemistry for sub-cellular fractions; sub-cellular resolution mass-spectrometry; and computational tools for analysis of sub-cellular genomics data. The new technologies developed by CSG will enable the broader genomics community to associate sub-cellular processes to cell function and dysfunction. These technologies will be utilized in the center to generate a comprehensive atlas of genomic signatures of sub-cellular compartments in the mammalian neuron system. The technologies and neuron-focused data obtained here will be relevant to neurodegenerative and neuropsychiatric diseases including schizophrenia, depression, autism spectrum disorder, traumatic brain injury, and Alzheimer's.

  Study phs002120

• Competitive selection of somatic mutant clones in normal human skin varies with body site

  The risk of getting non-melanoma skin cancer varies over 40-fold across the body. Here we map mutations in normal skin in high and low risk sites in normal donors and those with an increased risk of skin cancer. The density of mutations varied widely, with evidence of positive and negative genetic selection.  Regional differences in mutational signatures in high and low cancer risk sites and preferential selection of mutants of TP53 in high risk skin and FAT1 in lower risk skin were observed. 10% of clones had copy number changes in cancer associated genes and the largest had multiple driver mutations with loss of heterozygosity. In hair follicles, a proposed site of origin of skin cancers, mutations in the upper follicle resembled adjacent skin, but the lower follicle was sparsely mutated. We conclude cancer risk reflects the efficiency of transformation of oncogenic mutants rather than the density of mutant clones.

  Dataset EGAD00001006194

• MutWP5__CRUK_Mutographs_of_Cancer__Breast__Cancer_Mastectomy__WG_

  Sequencing of LCM-derived microbiopsies from 40 women who underwent mastectomies due to breast cancer. LCM and sequencing will be conducted on both normal, unaffected breast, and, where possible, tumour tissue. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue, and compare findings between the normal and associated cancer tissues. Whole-genome sequencing will be conducted on samples identified as promising from the initial targeted data. Results from this portion of the study will be compared to women who had cosmetic breast reduction surgeries and those who are BRCA carriers.

  Study EGAS00001003317

• Anaplastic_Meningioma_WGS_X10

  Anaplastic meningiomas are a rare, malignant variant of meningioma. At present there is no effective treatment for this cancer. The aim of the study is to identify somatic mutations in anaplastic meningiomas. We plan to sequence a set of 500 known cancer genes in 50 anaplastic meningioma and corresponding peripheral blood DNA samples. Bioinformatics will be used to analyse the results to assess the probability of these mutations being causal and so likely of critical importance for the tumour growth. Identification of these mutations will guide selection of appropriate compounds to effectively treat the disease.

  Study EGAS00001000859

• Non-small cell lung cancer proteome subtypes expose targetable oncogenic drivers and immune evasion mechanisms

  Proteome-level data of non-small cell lung cancer remains limited. In this study, we have collected 141 cases, and performed histological review, methylation profiling (113), custom panel sequencing (140), microarray expression profiling (118) and mass-spectrometry based proteomics (141). We identified six distinct groups of patients driven by histology, growth pattern, immune cell infiltration, druggable driver mutations, and hypomethylation-associated neoantigen burden. We validated the subtypes in independent proteomics datasets. Proteomics can refine treatment-oriented subtyping of non-small cell lung cancer.

  Study EGAS00001005482

• The ALT pathway generates telomere fusions that can be detected in the blood of cancer patients

  Telomere fusions (TFs) can trigger the accumulation of oncogenic alterations leading to malignant transformation and drug resistance. Despite their relevance in tumour evolution, our understanding of the patterns and consequences of TFs in human cancers remains limited. Here, we characterize the rates and spectrum of somatic TFs across >30 cancer types using whole-genome sequencing data. TFs are pervasive in human tumours with rates varying markedly across and within cancer types. In addition to end-to-end fusions, we find novel patterns of TFs that we mechanistically link to the activity of the alternative lengthening of telomeres (ALT) pathway. We show that TFs can be detected in the blood of cancer patients, which enables cancer detection with high specificity and sensitivity even for early-stage tumours and cancers of high unmet clinical need. Overall, we report a novel genomic footprint that enables characterization of the telomere maintenance mechanism of tumours and liquid biopsy analysis.

  Dataset EGAD00001012101

• Circulating tumour DNA abundance and potential utility in de novo metastatic prostate cancer

  Several systemic therapeutic options exist for metastatic castration sensitive prostate cancer (mCSPC). Circulating tumour DNA can profile metastatic castration resistant prostate cancer and influence treatment decisions, but remains untested in mCSPC. We set out to determine ctDNA abundance at de novo mCSPC diagnosis and whether ctDNA provides complementary clinically relevant information to a prostate biopsy. We collected and sequenced 77 plasma cell-free DNA samples from 53 newly diagnosed patients with mCSPC. Targeted sequencing was also performed on DNA from 48 diagnostic prostate tissue samples.

  Study EGAS00001003351

• 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

• Prediction of DNA Repair Inhibitor Response in Short Term Patient-Derived Ovarian Cancer Organoids

  In this study, 34 ovarian tumor organoids generated from 23 patients underwent paired DNA damage repair defect functional analyses and whole exome sequencing analysis to compare genetic mutational status to DNA repair functional capacity. 22 of the patients had high grade serous cancer and 1 of the patients had low grade serous cancer. A normal control, fresh parent tumor, and cells from the organoid culture generated from the parent tumor underwent whole exome sequencing analysis and the data from the sequencing analysis is provided here.

  Study phs001685

• The subclonal architecture of metastatic breast cancer: Results from a prospective community-based rapid autopsy program 'CASCADE'

  Background: Understanding the cancer genome is seen as a key step in improving outcomes for cancer patients. Genomic assays are emerging as a possible avenue to personalised medicine in breast cancer. The majority of work in this area has targeted primary tumours however, and very few studies have performed comprehensive profiling of advanced disease. Evolution of the cancer genome during the natural history of breast cancer is largely unknown, as is the profile of disease at death. We sought to study in detail these aspects of advanced breast cancers that have resulted in lethal disease. Methods and Findings: Three patients with ER-positive, HER2-negative breast cancer and one patient with triple negative breast cancer underwent rapid autopsy as part of an institutional prospective community-based rapid autopsy program. Cases represented a range of management problems in breast cancer, including late relapse after early stage disease; de novo metastatic disease; discordant disease response and disease refractory to treatment. Between 5 and 12 metastatic sites were collected at autopsy together with available primary tumours and longitudinal metastatic biopsies taken during life. Samples underwent paired tumour-normal whole exome sequencing and single nucleotide polymorphism arrays. Subclonal architectures were inferred by jointly analysing all samples from each patient. Mutations were validated using high depth amplicon sequencing.Between cases, there were significant differences in mutational burden, driver mutations, mutational processes and copy number variation. Within each case, we found dramatic heterogeneity in subclonal structure from primary to metastatic disease and between metastatic sites, such that no single lesion captured the breadth of disease. Metastatic cross seeding was found in each case and treatment drove subclonal diversification. Subclones displayed parallel evolution of treatment resistance in some cases, and apparent augmentation of key oncogenic drivers as an alternative resistance mechanism. We also observed the key role of mutational processes in subclonal evolution.Limitations of this study include the potential for bias introduced by joint analysis of formalin fixed archival specimens with fresh specimens, and the difficulties in resolving subclones with whole exome sequencing. Other alterations that could define subclones such as structural variants or epigenetic modifications were not assessed. Conclusions: This study highlights the variety of mechanisms that shape the genome of metastatic breast cancer, and the value of studying advanced disease in detail. Treatment drives significant genomic heterogeneity in breast cancers which has implications for disease monitoring and treatment selection in the personalised medicine paradigm.

  Study EGAS00001002153

• Dynamics of genomic clones in breast cancer patient xenografts at single cell resolution

  Dynamics of genomic clones in breast cancer patient xenografts at single cell resolution

  Dataset EGAD00001001066

• Exome sequencing data of 15 French Caucasian and 10 African-Caribbean men with prostate Cancer.

  Exome sequencing data of 15 French Caucasian and 10 African-Caribbean men with prostate Cancer.

  Dataset EGAD00001003306

• Germline whole exome sequencing in testicular cancer

  This dataset contains variant call format files generated from whole exome sequencing of germline DNA from indiviudals with diagnosed with testicualr germ cell cancer.

  Dataset EGAD00001004345

• Exome sequencing to evaluate HER2/ERBB2 mutations in cancer

  ERBB2/HER2 transmembrane and juxtamembrane domain mutations in cancer. Exome sequencing of tumor and matched blood and 2 blood samples from relatives.

  Dataset EGAD00001004351

• Sequence of breast cancer bone metastases PDX from 2 targeted panels

  Targeted sequencing analyses was made on samples of PDX engrafted with breast cancer bone metastases, 2 PDX acquired resistance to palbociclib.

  Dataset EGAD00001006070

• Whole genome sequencing of a breast cancer cohort with known functional homologous recombination status

  41 breast cancer patients with known functional homologous recombination status (matched normal and tumor genomes, n=82)

  Dataset EGAD00001008027

• Whole Exome Sequencing of Localized Prostate Cancer Patients

  Whole exome sequencing of localized prostate cancer patients in this study contained pair tumor-normal samples and validated tumor content.

  Dataset EGAD00001008274

• whole genome sequencing of breast cancer cell lines and patient derived xenograft models

  whole genome sequencing of six commonly used breast cancer cell lines and six patient derived xenograft models

  Dataset EGAD00001008802

• Treated and control Patient Derived Xenografts of colorectal cancer (CRC) samples

  Bank of treateed and control PDXs metastastic colorectal cancer sample RNAseq

  Dataset EGAD00001010022

• Molecular analysis of cancer genomes in children with Lynch syndrome: exploring causal associations WXS

  Molecular analysis of cancer genomes in children with Lynch syndrome: exploring causal associations WXS

  Dataset EGAD00001010043

• Multi-omics Profiling of Asian Breast Cancers

  Whole exome and transcriptome sequencing data of primary tumors from 178 Korean breast cancer patients.

  Study EGAS00001002621