Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genotyping of human glioma - assessing the significance of chromosomal aberrations in cancer

ABSTRACT: Comprehensive knowledge of the genomic alterations that underlie cancer is a critical foundation for diagnostics, prognostics and targeted therapeutics. Systematic efforts to analyze cancer genomes are underway, but the analysis is hampered by the lack of a statistical framework to distinguish meaningful events from random background aberrations. Here, we describe a systematic method called Genomic Identification of Significant Targets in Cancer (GISTIC) designed for analyzing chromosomal aberrations in cancer. We use it to study chromosomal aberrations in 141 gliomas and compare the results with two prior studies. Traditional methods highlight hundreds of altered regions with little concordance between studies. The new approach reveals a highly concordant picture involving ~35 significant events, including 16-18 broad events near chromosome-arm size and 16-21 focal events. About half of these events correspond to known cancer-related genes, only some of which have been previously tied to glioma. We also show that superimposed broad and focal events may have different biological consequences. Specifically, gliomas with broad amplification of chromosome 7 have different properties than those with overlapping focal EGFR amplification: the broad events act in part through effects on MET and its ligand HGF and correlate with MET dependence in vitro. Our results support the feasibility and utility of systematic characterization of the cancer genome. Experiment Overall Design: 141 gliomas and 33 normal tissue samples were subject to 100K SNP analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: Rameen Beroukhim

PROVIDER: E-GEOD-9635 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Assessing the significance of chromosomal aberrations in cancer: methodology and application to glioma.

Beroukhim Rameen R Getz Gad G Nghiemphu Leia L Barretina Jordi J Hsueh Teli T Linhart David D Vivanco Igor I Lee Jeffrey C JC Huang Julie H JH Alexander Sethu S Du Jinyan J Kau Tweeny T Thomas Roman K RK Shah Kinjal K Soto Horacio H Perner Sven S Prensner John J Debiasi Ralph M RM Demichelis Francesca F Hatton Charlie C Rubin Mark A MA Garraway Levi A LA Nelson Stan F SF Liau Linda L Mischel Paul S PS Cloughesy Tim F TF Meyerson Matthew M Golub Todd A TA Lander Eric S ES Mellinghoff Ingo K IK Sellers William R WR

Proceedings of the National Academy of Sciences of the United States of America 20071206 50

Comprehensive knowledge of the genomic alterations that underlie cancer is a critical foundation for diagnostics, prognostics, and targeted therapeutics. Systematic efforts to analyze cancer genomes are underway, but the analysis is hampered by the lack of a statistical framework to distinguish meaningful events from random background aberrations. Here we describe a systematic method, called Genomic Identification of Significant Targets in Cancer (GISTIC), designed for analyzing chromosomal aber ...[more]

PMID: 18077431

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Dataset Information

Genotyping of human glioma - assessing the significance of chromosomal aberrations in cancer

Publications

Assessing the significance of chromosomal aberrations in cancer: methodology and application to glioma.

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