title: Functional copy-number alterations in cancer.
abstract: Understanding the molecular basis of cancer requires characterization of its genetic defects. DNA microarray technologies can provide detailed raw data about chromosomal aberrations in tumor samples. Computational analysis is needed (1) to deduce from raw array data actual amplification or deletion events for chromosomal fragments and (2) to distinguish causal chromosomal alterations from functionally neutral ones. We present a comprehensive computational approach, RAE, designed to robustly map chromosomal alterations in tumor samples and assess their functional importance in cancer. To demonstrate the methodology, we experimentally profile copy number changes in a clinically aggressive subtype of soft-tissue sarcoma, pleomorphic liposarcoma, and computationally derive a portrait of candidate oncogenic alterations and their target genes. Many affected genes are known to be involved in sarcomagenesis; others are novel, including mediators of adipocyte differentiation, and may include valuable therapeutic targets. Taken together, we present a statistically robust methodology applicable to high-resolution genomic data to assess the extent and function of copy-number alterations in cancer.
authors.affiliation: Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America. copy-number@cbio.mskcc.org
authors.forename: Barry S
authors.initials: BS
authors.lastname: Taylor
authors.forename: Jordi
authors.initials: J
authors.lastname: Barretina
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Socci
authors.forename: Penelope
authors.initials: P
authors.lastname: Decarolis
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.forename: Samuel
authors.initials: S
authors.lastname: Singer
authors.forename: Chris
authors.initials: C
authors.lastname: Sander
mesh_terms: D002869:Chromosome Aberrations; D016000:Cluster Analysis; D005784:Gene Amplification; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D023281:Genomics / Q000379:methods*; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D009369:Neoplasms / Q000235:genetics*; D010641:Phenotype; D016012:Poisson Distribution; D020641:Polymorphism, Single Nucleotide
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