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Comparative oncogenomic analysis of copy number alterations in human and zebrafish tumors enables cancer driver discovery

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Item Type:Article
Title:Comparative oncogenomic analysis of copy number alterations in human and zebrafish tumors enables cancer driver discovery
Creators Name:Zhang, G. and Hoersch, S. and Amsterdam, A. and Whittaker, C.A. and Beert, E. and Catchen, J.M. and Farrington, S. and Postlethwait, J.H. and Legius, E. and Hopkins, N. and Lees, J.A.
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.
Keywords:Aneuploidy, Chromosome Aberrations, DNA Copy Number Variations, Neoplastic Gene Expression Regulation, Neoplasm Genes, Human Genome, Genomics, High-Throughput Nucleotide Sequencing, Neurilemmoma, Oligonucleotide Array Sequence Analysis, Animals, Zebrafish
Source:PLoS Genetics
ISSN:1553-7404
Publisher:Public Library of Science (U.S.A.)
Volume:9
Number:8
Page Range:e1003734
Date:August 2013
Official Publication:https://doi.org/10.1371/journal.pgen.1003734
PubMed:View item in PubMed

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