Dataset Information

Whole Genomic Sequencing of Nine Primary Colorectal Adenocarcinoma Tumor/Germline Pairs

ABSTRACT:

This study was the first-known effort to complete the complete genome sequencing of primary colorectal adenocarcinomas and the matched germline genome. Nine colorectal adenocarcinomas selected on the basis of having chromosomal instability were subjected to 'shotgun' Illumina sequencing with 101-bp paired end reads to an approximate goal of 30x coverage of tumor and of normal. From these sequences, we used various computational techniques to identify somatic point mutations, insertion/deletions and structural rearrangements in these tumors. From these data, we identified new insights into the rates of background mutations in these cancers, new spectrums of structural alterations including the identification of a novel in-frame fusion gene.

PROVIDER: phs000374.v1.p1 | EGA |

REPOSITORIES: EGA

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Publications

Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion.

Bass Adam J AJ Lawrence Michael S MS Brace Lear E LE Ramos Alex H AH Drier Yotam Y Cibulskis Kristian K Sougnez Carrie C Voet Douglas D Saksena Gordon G Sivachenko Andrey A Jing Rui R Parkin Melissa M Pugh Trevor T Verhaak Roel G RG Stransky Nicolas N Boutin Adam T AT Barretina Jordi J Solit David B DB Vakiani Evi E Shao Wenlin W Mishina Yuji Y Warmuth Markus M Jimenez Jose J Chiang Derek Y DY Signoretti Sabina S Kaelin William G WG Spardy Nicole N Hahn William C WC Hoshida Yujin Y Ogino Shuji S DePinho Ronald A RA Chin Lynda L Garraway Levi A LA Fuchs Charles S CS Baselga Jose J Tabernero Josep J Gabriel Stacey S Lander Eric S ES Getz Gad G Meyerson Matthew M

Nature genetics 20110904 10

Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma and have surveyed exons of protein-coding genes for mutations in 11 affected individuals. Here we report whole-genome sequencing from nine individuals with colorectal cancer, including primary colorectal tumors and matched adjacent non-tumor tissues, at an average of 30.7× and 31.9× coverage, respectively. We identify an average of 75 somatic rearrangements per tumor, including complex networks of translocat ...[more]

PMID: 21892161

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Project description:Pulmonary enteric adenocarcinoma (PEAD) is a rare non-small cell lung cancer subtype. It is poorly characterized and cannot be distinguished from metastatic colorectal or upper gastrointestinal adenocarcinomas (ADCs) by means of routine pathological methods. As DNA methylation patterns are known to be highly tissue specific, we aimed to develop a methylation-based algorithm to differentiate these entities. To this end, genome wide methylation profiles of 600 primary pulmonary, colorectal and upper gastrointestinal ADCs obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database were used as a reference cohort to train a machine learning algorithm. The resulting classifier correctly classified all samples from a validation cohort consisting of 680 primary pulmonary, colorectal and upper gastrointestinal ADCs from TCGA and the GEO database, demonstrating the ability of the algorithm to reliably distinguish these three entities. We then analyzed DNA methylation data of 15 PEADs as well as four pulmonary metastases and four primary colorectal ADCs with the algorithm. All 15 PEADs were reliably classified as primary pulmonary tumors and all four metastases as well as all four primary colorectal ADC samples were identified as primary colorectal ADCs. In a t-distributed stochastic neighbor embedding analysis, the PEAD samples did not form a separate methylation subclass but rather diffusely intermixed with other pulmonary ADCs. Additional characterization of the PEAD series using fluorescence in-situ hybridization, next generation sequencing and copy number analysis revealed KRAS mutations in nine of 15 samples (60%) and a high number of structural chromosomal changes. Except for an unusually high rate of chromosome 20 gain (66.7%) the molecular data was mostly reminiscent of standard pulmonary ADCs. In conclusion, we provide sound evidence of the pulmonary origin of PEAD and in addition provide a publicly available machine learning based algorithm to reliably distinguish PEAD from metastatic colorectal cancer and upper gastrointestinal adenocarcinomas.

Dataset Information

Whole Genomic Sequencing of Nine Primary Colorectal Adenocarcinoma Tumor/Germline Pairs

Publications

Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion.

Similar Datasets

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