Genome and transcriptome sequencing of lung cancers reveal diverse mutational and splicing events [array component]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE40908 | GEO | 2012/09/26
SECONDARY ACCESSION(S): PRJNA176024
REPOSITORIES: GEO
Similar Datasets
Project description:Lung cancer is a highly heterogeneous disease in terms of both underlying genetic lesions and response to therapeutic treatments. We performed deep whole genome sequencing and transcriptome sequencing on 19 lung cancer cell lines and 3 lung tumor/normal pairs (provisional dbGaP accession number; phs000299.v2.p1). Overall, our data show that cell line models exhibit similar mutation spectra to human tumor samples. Taken together, these data present a comprehensive genomic landscape of a large number of lung cancer samples and further demonstrate that cancer specific alternative splicing is a widespread phenomenon that has potential utility as therapeutic biomarkers. Nineteen non-small cell lung cancer cell lines were assayed for genotype, copy number and LOH using Illumina Omni2.5-4 arrays, GenomeStudio V2011.1, and a modified version of the PICNIC (PMID 19837654) algorithm.
2012-09-26 | E-GEOD-40908 | biostudies-arrayexpress
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2013-02-11 | E-GEOD-42363 | biostudies-arrayexpress
Project description:Understanding the molecular signatures of cancer is important to apply appropriate targeted therapies. Here we present the first large scale RNA sequencing study of lung adenocarcinoma demonstrating its power to identify somatic point mutations as well as transcriptional variants such as gene fusions, alternative splicing events and expression outliers. Our results reveal the genetic basis of 200 lung adenocarcinomas in Koreans including deep characterization of 87 surgical specimens by transcriptome sequencing. We identified driver somatic mutations in cancer genes including EGFR, KRAS, NRAS, BRAF, PIK3CA, MET and CTNNB1. New cancer genes, such as LMTK2, ARID1A, NOTCH2 and SMARCA4, were also suggested as candidates for novel drivers in lung adenocarcinoma. We found 45 fusion genes, 8 of which were chimeric tyrosine kinases involving ALK, RET, ROS1, FGFR2, AXL and PDGFRA. Of 17 recurrent alternative splicing events, we identified exon 14 skipping in the proto-oncogene MET as highly likely to be a cancer driver. The number of somatic mutations and expression outliers varied markedly between individual cancers and was strongly correlated with smoking history of cancer patients. In addition, we identified genomic blocks where genes were frequently up- or down-regulated together that could be explained by copy number alterations in the cancer tissue. We also found an association between lymph node metastasis and somatic mutations in TP53. Our findings broaden our understanding of lung adenocarcinoma and may also lead to new diagnostic and therapeutic approaches. * Raw data files were submitted to EBI-SRA under accession number ERP001058.
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2014-12-20 | E-GEOD-64144 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. The raw sequencing data is available through dbGaP (controlled access) due to patient privacy concerns. https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001961.v1.p1
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2015-09-10 | E-GEOD-60982 | biostudies-arrayexpress
Project description:We performed RRBS and WGBS on primary human chronic lymphocytic leukemia and normal healthy donor B cell samples Due to patient privacy concerns, the raw data is being made available via controlled access in dbGaP (http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000435.v1.p1).
2015-01-01 | GSE58889 | GEO
Project description:<p>Version 1</p> <p>Whole genome sequencing was applied to tumor and adjacent normal lung tissue in an individual non-small-cell lung cancer patient. We present an analysis of somatic changes identified throughout the tumor genome, including single-nucleotide variants, copy number variants, and large-scale chromosomal rearrangements. Over 50,000 high-confidence single-nucleotide variants were identified, revealing evidence of substantial smoking-related DNA damage as well as distinct mutational pressures within the tumor resulting in uneven distribution of somatic mutations across the genome.</p> <p>Version 2</p> <p>Lung cancer is a highly heterogeneous disease in terms of both underlying genetic lesions and response to therapeutic treatments. We performed deep whole genome sequencing and transcriptome sequencing on 19 lung cancer cell lines and 3 lung tumor/normal pairs. Overall, our data show that cell line models exhibit similar mutation spectra to human tumor samples. Smoker and never-smoker cancer samples exhibit distinguishable patterns of mutations. A number of epigenetic regulators are frequently altered by mutations or copy number changes. A systematic survey of splice-site mutations identified over 100 splice site mutations associated with cancer specific aberrant splicing, including mutations in several known cancer-related genes. Differential usages of splice isoforms were also studied. Taken together, these data present a comprehensive genomic landscape of a large number of lung cancer samples and further demonstrate that cancer specific alternative splicing is a widespread phenomenon that has potential utility as therapeutic biomarkers.</p>
| phs000299 | dbGaP
Project description:We performed RRBS and WGBS on primary human chronic lymphocytic leukemia and normal healthy donor B cell samples Due to patient privacy concerns, the raw data is being made available via controlled access in dbGaP (http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000435.v1.p1). cross-sectional/longitudinal
2015-01-01 | E-GEOD-58889 | biostudies-arrayexpress
Project description:The Genotype-Tissue Expression (GTEx) project is a collaborative effort that aims to identify correlations between genotype and tissue-specific gene expression levels that will help identify regions of the genome that influence whether and how much a gene is expressed. GTEx is funded through the Common Fund, and managed by the NIH Office of the Director in partnership with the National Human Genome Research Institute, National Institute of Mental Health, the National Cancer Institute, the National Center for Biotechnology Information at the National Library of Medicine, the National Heart, Lung and Blood Institute, the National Institute on Drug Abuse, and the National Institute of Neurological Diseases and Stroke, all part of NIH. This series of 837 samples represents multiple tissues collected from 102 GTEX donors and 1 control cell line. In total, 30 tissue sites are represented including Adipose, Artery, Heart, Lung, Whole Blood, Muscle, Skin, and 11 brain subregions. RNA-seq expression data, robust clinical data, pathological annotations, and genotypes are also available for these samples from dbGaP (http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000424.v2.p1) and the GTEx portal (www.broadinstitute.org/gtex). While GTEx is no longer generating Affymetrix expression data, donor enrollment continues and is expected to reach 1,000 by the end of 2015. Updates to the GTEx data in dbGaP and the GTEx Portal will be made periodically. contributor: GTEx Laboratory, Data Analysis, and Coordinating Center (LDACC) contributor: The Broad Institute of MIT and Harvard (LDACC PIs: Kristin Ardlie and Gaddy Getz) GTEx samples are collected from deceased donors at low post-mortem intervals and preserved in PAXgene fixative prior to DNA and RNA extraction.
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