Spliceosomal factor mutations and mis-splicing in MDS.

Somatic, heterozygous missense and nonsense mutations in at least seven proteins that function in the spliceosome are found at high frequency in MDS patients. These proteins act at various steps in the process of splicing by the spliceosome and lead to characteristic alterations in the alternative splicing of a subset of genes. Several studies have investigated the effects of these mutations and have attempted to identify a commonly affected gene or pathway. Here, we summarize what is known about the normal function of these proteins and how the mutations alter the splicing landscape of the genome. We also summarize the commonly mis-spliced gene targets and discuss the state of mechanistic unification that has been achieved. Finally, we discuss alternative mechanisms by which these mutations may lead to disease.