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.