A large database of copy number profiles from
cancer genomes can facilitate the identification of recurrent chromosomal alterations that often contain key
cancer-related genes. It can also be used to explore low-prevalence genomic events such as
chromothripsis. In this study, we report an analysis of 8227 human
cancer copy number profiles obtained from 107 array comparative genomic hybridization (CGH) studies. Our analysis reveals similarity of chromosomal arm-level alterations among developmentally related
tumor types as well as a number of co-occurring pairs of arm-level alterations. Recurrent ("pan-lineage") focal alterations identified across diverse
tumor types show an enrichment of known
cancer-related genes and genes with relevant functions in
cancer-associated phenotypes (e.
g., kinase and cell cycle).
Tumor type-specific ("lineage-restricted") alterations and their enriched functional categories were also identified. Furthermore, we developed an algorithm for detecting regions in which the copy number oscillates rapidly between fixed levels, indicative of
chromothripsis. We observed these massive genomic rearrangements in 1%-2% of the samples with variable
tumor type-specific incidence rates. Taken together, our comprehensive view of copy number alterations provides a framework for understanding the functional significance of various genomic alterations in
cancer genomes.