Cancer Program Publication

Assessing the significance of chromosomal aberrations in cancer: Methodology and application to glioma
ProjectBrain Cancer
Additional Projects/
Categories
SNP Analysis
Bioinformatics & Computational Biology
AbstractComprehensive knowledge of the genomic alterations that underlie cancer is a critical foundation for diagnostics, prognostics and targeted therapeutics. Analyses of chromosomal aberrations are 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). We use it to study chromosomal aberrations in 141 gliomas and compare the results with two prior studies. Traditional methods show little concordance between these studies and highlight hundreds of altered regions. 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 need not have the same target. 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.
AuthorsRameen 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 Mischel, Tim F. Cloughesy, Matthew Meyerson, Todd R. Golub, Eric S. Lander, Ingo K. Mellinghoff, William R. Sellers
Publication Date12/11/2007
Contact emails rameen@broad.mit.edu
gadgetz@broad.mit.edu
Publication URLhttp://www.pnas.org/cgi/reprint/0710052104v1
Citation Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):20007-12
Keywordssingle-nucleotide polymorphism arrays; bioinformatics; glioblastoma; comparative genomic hybridization; copy-number alterations
 
Supplemental Information
URLs
NameURL
Expression Files (272 MB)ftp://ftp.broad.mit.edu/pub/gistic/Expression.zip
Affymetrix 50K Hind chip files (2.6 GB)ftp://ftp.broad.mit.edu/pub/gistic/Hind.zip
Affymetrix 50K Xba chip files (2.7 GB)ftp://ftp.broad.mit.edu/pub/gistic/Xba.zip
Signal intensities & genotypes for all Hind samples (45 MB)ftp://ftp.broad.mit.edu/pub/gistic/Hind_summary.zip
Signal intensities & genotypes for all Xba samples (46 MB)ftp://ftp.broad.mit.edu/pub/gistic/Xba_summary.zip
Files
DescriptionFile
ManuscriptGISTIC_071020.pdf
Supplemental InformationGISTIC_Supplement_071020.pdf
Segmented Datasegmented_data_080520.seg
Array List File for GISTICGlioma_array_list_080423.txt
Copy-number Polymorphisms (100K SNP only)100K_CNVs_080423.txt
Marker Positions100K_markerpositions.hg16.txt
Sample information (txt format)Sample_info_070424.txt
Array List File for GISTICPreprocessingGliomas_normals_array_list_080522.txt
GISTIC FAQGISTIC FAQ_090320.htm
GISTICPreprocessing for 64-bit LinuxPREPROCESSING.tar.gz
GISTIC for 64-bit LinuxGISTIC_0_9_2.tar.gz