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PMID: 21129771 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

An integrated approach to uncover drivers of cancer.

Cell ·Vol. 143 ·No. 6 ·2010-12-10 ·Pages 1005-17

Akavia UD, Litvin O, Kim J, Sanchez-Garcia F, Kotliar D, Causton HC, Pochanard P, Mozes E, Garraway LA, Pe'er D

Abstract

Systematic characterization of cancer genomes has revealed a staggering number of diverse aberrations that differ among individuals, such that the functional importance and physiological impact of most tumor genetic alterations remain poorly defined. We developed a computational framework that integrates chromosomal copy number and gene expression data for detecting aberrations that promote cancer progression. We demonstrate the utility of this framework using a melanoma data set. Our analysis correctly identified known drivers of melanoma and predicted multiple tumor dependencies. Two dependencies, TBC1D16 and RAB27A, confirmed empirically, suggest that abnormal regulation of protein trafficking contributes to proliferation in melanoma. Together, these results demonstrate the ability of integrative Bayesian approaches to identify candidate drivers with biological, and possibly therapeutic, importance in cancer.

MeSH Terms
Bayes Theorem GTPase-Activating Proteins/genetics,metabolism Gene Expression Profiling Humans Melanoma/genetics Microphthalmia-Associated Transcription Factor/genetics,metabolism Protein Transport rab GTP-Binding Proteins/genetics,metabolism rab27 GTP-Binding Proteins
Chemicals
GTPase-Activating Proteins MITF protein, human Microphthalmia-Associated Transcription Factor TBC1D16 protein, human rab27 GTP-Binding Proteins RAB27A protein, human rab GTP-Binding Proteins
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Akavia Uri David
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Litvin Oren
Kim Jessica
Sanchez-Garcia Felix
Kotliar Dylan
Causton Helen C
Pochanard Panisa
Mozes Eyal
Garraway Levi A
Pe'er Dana
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2010.11.013
Published
2010-12-10
Epub
2010-00-02
Pages
1005-17
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC3013278
Subset
IM
Grants
NIH HHS · DP2 OD002414-01 · United States
NIH HHS · 1-DP2-OD002414-01 · United States
NCI NIH HHS · U54 CA121852-06 · United States
NIH HHS · DP2 OD002414 · United States
NCI NIH HHS · 1U54CA121852-01A1 · United States
NCI NIH HHS · U54 CA121852 · United States
Databases
GEO
GSE23884
Corrections
CommentIn
PMID: 21322290
External Links
PubMed source DOI: 10.1016/j.cell.2010.11.013 PMC Full Text View journal details
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