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

• DOI: 10.1073/pnas.0710052104
• Publication Date: 2007-12-07T01:44:47Z
• Authors: Rameen Beroukhim; Gad Getz; Leia Nghiemphu; Jordi Barretina; Teli Hsueh; David Linhart; Igor Vivanco; Jeffrey C. Lee; Julie H. Huang; Sethu Alexander; Jinyan Du; Tweeny Kau; Roman K. Thomas; Kinjal Shah; Horacio Soto; Sven Perner; John Prensner; Ralph M. Debiasi; Francesca Demichelis; Charlie Hatton; Mark A. Rubin; Levi A. Garraway; Stan F. Nelson; Linda Liau; Paul S. Mischel; Tim F. Cloughesy; Matthew Meyerson; Todd A. Golub; Eric S. Lander; Ingo K. Mellinghoff; William R. Sellers
• Keywords: Concordance

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