Cancer genomes may contain a wide array of aberrations—point mutations, small insertions and deletions, genomic rearrangements and viral-genome insertions—all of which can be detected by deep sequencing of tumor samples. However, we are only just beginning to understand how to use such data to study the processes underlying oncogenesis. In a recent paper in Nature Biotechnology, Carter et al.1 show that quantifying copy
number changes and point mutations on an absolute, rather than relative, scale facilitates the identification of oncogenes and tumor suppressors and provides insight into the subclonal architecture of tumors and into tumor evolution. Analytical approaches such as this should be useful for interpreting data from large cancer genome sequencing projects and from individual genomes sequenced as part of clinical care.
Copy number analysis represents arguably the simplest view on the cancer genome. Since the 1960s, it has been possible to count the number of copies of a chromosome or of large chromosomal regions in cancer cells using cytogenetic techniques such as karyotyping. The resolution of copy number detection has increased greatly with newer methods that compare tumor and normal genomes by comparative genomic hybridization to microarrays2 or by massively parallel sequencing. These methods have identified several recurrent