Spliceosomal gene mutations in myelodysplasia: molecular links to clonal abnormalities of hematopoiesis
Year: 2016
Type: preprint
Abstract: Genomic analyses of the myeloid malignancies and clonal disorders of hematopoiesis that may give rise to these disorders have identified that mutations in genes encoding core spliceosomal proteins and accessory regulatory splicing factors are among the most common targets of somatic mutations. These spliceosomal mutations often occur in a mutually exclusive manner with one another and, in aggregate, account for the most frequent class of mutations in patients with myelodysplastic syndromes (MDSs) in particular. Although substantial progress has been made in understanding the effects of several of these mutations on splicing and splice site recognition, functional connections linking the mechanistic changes in splicing induced by these mutations to the phenotypic consequences of clonal and aberrant hematopoiesis are not yet well defined. This review describes our current understanding of the mechanistic and biological effects of spliceosomal gene mutations in MDSs as well as the regulation of splicing throughout normal hematopoiesis.
Source: Genes & Development
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Funders: U.S. Department of Defense, Ellison Medical Foundation, Damon Runyon Cancer Research Foundation, Memorial Sloan-Kettering Cancer Center, Edward P. Evans Foundation, Starr Foundation, Yasuda Memorial Medical Foundation, Kanae Foundation for the Promotion of Medical Science, National Institutes of Health, Japan Society for the Promotion of Science, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1199881869, G271495716, G294469890, G3229767079, UNDERSTANDING THE TARGETING EPIGENETIC ALTERATIONS IN AQUIRED BONW MARROW FAILURE, G4119534169, Role of ASXL1 mutations in myeloid malignancies, U2AF1 mutations in myelodysplastic syndromes: from mechanism to therapy, G5850682332, G887357334, Cancer Center Support Grant, Genetic and molecular basis for SRSF2 mutations in myelodysplasia
OpenAlex ID: W2346350699