Studies of genomic copy number changes in human cancers reveal signatures of DNA replication stress

Human cancers are characterized by the presence of genomic instability. Recently, two studies have catalogued the presence of a specific class of genomic aberrations, large deletions and insertions, in a few thousand human cancers and reported that most of the prevalent recurrent focal deletions targeted common fragile sites and large genes. In various experimental systems, deletions in common fragile sites and large genes have been linked to the presence of DNA replication stress. Thus, taken together, these results suggest the presence of DNA replication stress in human cancers, consistent with the recently proposed oncogene-induced DNA damage model for cancer development.

► High throughput studies characterizing genomic instability in human cancers were reviewed. ► The most frequent deletions in human cancers target the common fragile sites. ► DNA replication stress induces deletions in common fragile sites. ► Oncogenes induce DNA replication stress. ► Thus, oncogene-induced DNA replication stress induces genomic instability in human cancers.