Rare and private spliceosomal gene mutations drive partial, complete, and dual phenocopies of hotspot alterations.

ABSTRACT: Genes encoding the RNA splicing factors SF3B1, SRSF2, and U2AF1 are subject to frequent missense mutations in clonal hematopoiesis and diverse neoplastic diseases. Most "spliceosomal" mutations affect specific hotspot residues, resulting in splicing changes that promote disease pathophysiology. However, a subset of patients carries spliceosomal mutations that affect non-hotspot residues, whose potential functional contributions to disease are unstudied. Here, we undertook a systematic characterization of diverse rare and private spliceosomal mutations to infer their likely disease relevance. We used isogenic cell lines and primary patient materials to discover that 11 of 14 studied rare and private mutations in SRSF2 and U2AF1 induced distinct splicing alterations, including partially or c

SUBMITTER: Pangallo J 

PROVIDER: S-EPMC7099330 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature