Oncogenic Landscapes of Splicing-Factor Mutant MDS

Authors:

Rahman MA*

Volume 2, Issue 1

Abstract

Genomic analyses of the myeloid malignancies surprisingly identified recurrent heterozygous somatic mutations in several splicing factors. Among them, SF3B1, SRSF2, U2AF1 and ZRSR2 are most frequently mutated in patients with myelodysplastic syndrome (MDS). Recent studies suggest that mutations in SRSF2 and U2AF1 alter their normal RNA binding and splicing preferences in a sequence-specific manner, whereas mutations in SF3B1 promote selection of cryptic 3’ splice sites. In contrast, mutations in ZRSR2 affect splicing of U12-types introns in “minor spliceosome” pathway. Different mutations appear to regulate hundreds of different splicing targets, thereby exclude the possibility of common downstream splicing alterations. Therefore, it is important to focus on common physiological processes contributed to MDS etiology, which are coupled with splicing alterations promoted by different splicing factor mutations. This mini review summarizes the accumulating knowledge about the oncogenic splicing landscapes, underlying mechanisms, and physiological processes affected by mutations in three major factors, SRSF2, SF3B1 and U2AF1.

Keywords:

Oncogenic Landscapes; Genetic screenings

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