Comparative Oncogenomic Analysis of Copy Number Alterations in Human and Zebrafish Tumors Enables Cancer Driver Discovery
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Zhang-2013-Comparative oncogeno.pdf
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Author(s)
Zhang, GuangJun
Hoersch, Sebastian
Amsterdam, Adam
Whittaker, Charles A.
Beert, Eline
Catchen, Julian M.
Postlethwait, John H.
Legius, Eric
Farrington, Sarah M.
Hopkins, Nancy H.
Date Issued
August 2013
Journal
PLoS Genetics
Publisher
Public Library of Science
Citation
Zhang, GuangJun, Sebastian Hoersch, Adam Amsterdam, Charles A. Whittaker, Eline Beert, Julian M. Catchen, Sarah Farrington, et al. “Comparative Oncogenomic Analysis of Copy Number Alterations in Human and Zebrafish Tumors Enables Cancer Driver Discovery.” Edited by Marshall S. Horwitz. PLoS Genetics 9, no. 8 (August 29, 2013): e1003734.
Version
Final published version
Abstract
The identification of cancer drivers is a major goal of current cancer research. Finding driver genes within large chromosomal events is especially challenging because such alterations encompass many genes. Previously, we demonstrated that zebrafish malignant peripheral nerve sheath tumors (MPNSTs) are highly aneuploid, much like human tumors. In this study, we examined 147 zebrafish MPNSTs by massively parallel sequencing and identified both large and focal copy number alterations (CNAs). Given the low degree of conserved synteny between fish and mammals, we reasoned that comparative analyses of CNAs from fish versus human MPNSTs would enable elimination of a large proportion of passenger mutations, especially on large CNAs. We established a list of orthologous genes between human and zebrafish, which includes approximately two-thirds of human protein-coding genes. For the subset of these genes found in human MPNST CNAs, only one quarter of their orthologues were co-gained or co-lost in zebrafish, dramatically narrowing the list of candidate cancer drivers for both focal and large CNAs. We conclude that zebrafish-human comparative analysis represents a powerful, and broadly applicable, tool to enrich for evolutionarily conserved cancer drivers.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1371/journal.pgen.1003734
