Pan-cancer analysis identifies mutations in <i>SUGP1</i> that recapitulate mutant SF3B1 splicing dysregulation
Zhaoqi Liu, Jian Zhang, Yiwei Sun, Tomin E. Perea-Chamblee, James L. Manley, Raúl Rabadán
Abstract
Significance SF3B1 is the most commonly mutated splicing factor in cancers, and SF3B1 mutations result in aberrant 3′ splice site usage during splicing of a subset of introns. Here, we utilized an unbiased computational biology approach to determine whether cancer-associated mutations in any other genes produce the same pattern of aberrant splicing as do SF3B1 mutations. We found that, while rare, the most frequently mutated gene that causes such splicing defects is SUGP1 . This is striking because previous biochemical studies indicated that loss of SF3B1 interaction with SUGP1 underlies the effects of SF3B1 mutations on splicing. Our findings thus establish the cancer relevance of the biochemical link between SF3B1 and SUGP1 and also identify SUGP1 as a cancer-associated gene.