Cited by 484Cancer Genomics and DiagnosticsChromatin Remodeling and CancerGenomic variations and chromosomal abnormalities

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An Integrated Approach to Uncover Drivers of Cancer

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Akavia, Uri David, Litvin, Oren, Kim, Jessica, Sanchez-Garcia, Felix, Kotliar, Dylan, Causton, Helen C., Pochanard, Panisa, Mozes, Eyal, Garraway, Levi A., Pe'er, Dana·2010·Cell

DOI 10.1016/j.cell.2010.11.013PMC PMC3013278

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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.

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Authors: Akavia, U. D., Litvin, O., Kim, J., Sanchez-Garcia, F., Kotliar, D., Causton, H. C., Pochanard, P., Mozes, E., Garraway, L. A., & Pe'er, D.
Affiliations: Columbia University (US)
Broad Institute (US)
ORCID: Akavia, Uri David
Kim, Jessica
Kotliar, Dylan
Causton, Helen C.
Garraway, Levi A.
Venue: Cell
Publisher: Elsevier BV
Published: 2010-12
Volume: 143
Issue: 6
Pages: 1005-1017
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2010.11.013
PMC: PMC3013278
OpenAlex: W1968667083
Cited by: 484
References: 129
Citations by year: 2026: 5 · 2025: 5 · 2024: 14 · 2023: 21 · 2022: 18 · 2021: 17 · 2020: 30 · 2019: 28 · 2018: 24 · 2017: 33 · 2016: 42 · 2015: 51 · 2014: 47 · 2013: 60 · 2012: 56
FWCI: 14.99
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 959 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Burroughs Wellcome Fund
National Institutes of Health (DP2OD002414)
National Cancer Institute (U54CA121852)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
Keywords: cancer driver genes, melanoma, chromosomal copy number alterations, gene expression, tumor dependency, Rab27a, protein trafficking, tumor progression, therapeutic target
MeSH terms: rab27 GTP-Binding Proteins, Bayes Theorem, Humans, Melanoma, GTPase-Activating Proteins, rab GTP-Binding Proteins, Gene Expression Profiling, Protein Transport, Microphthalmia-Associated Transcription Factor

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An Integrated Approach to Uncover Drivers of Cancer

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