Our paper led by the former summer student Soumil Narayan was recently published in Genome Medicine. We investigated the cancer mutations affecting two types of important protein post-translational modifications (PTMs), acetylation and ubiquitination. These PTMs act as molecular switches of proteins and are known to be involved chromatin regulation in histones and general protein degradation, respectively. It turns out that somatic cancer mutations precisely modify many protein sites where PTMs occur, including known cancer driver genes such as PTEN, TP53, IDH1, and other less-recognised candidate genes such as the splicing factor SF3B1. Evidence also suggests that PTM-associated mutations often correlate with poor prognosis of cancer patients. Our analysis demonstrates an innovative way of exploring the mechanisms of cancer mutations to understand cancer biology and design cancer treatments. In particular, new drugs are now developed to modify acetylation and ubiquitination pathways so further analysis and experiments may reveal precision treatment strategies for patients whose tumors carry these PTM-associated mutations.
Frequent mutations in acetylation and ubiquitination sites suggest novel driver mechanisms of cancer
Soumil Narayan, Gary D. Bader and Jüri Reimand
Genome Medicine | 201 | 68:55 | DOI: 10.1186/s13073-016-0311-2