Telomerase Gene Complex Mutations Are Common In Myelodysplastic Syndromes Patients

Telomerase complex maintains telomeres and protects genomic DNA from degradation during cell divisions. Abnormal telomerase function can result in chromosomal instability predisposing to malignant transformation. Short telomere is a typical feature of inherited bone marrow failures syndromes (BMFs), especially dyskeratosis congenital (DC), caused by mutations in genes encoding components of the telomerase gene complex (TGC), shelterin proteins and DNA helicases. Telomere attrition have been associated with leukemic transformation in myelodysplastic syndromes (MDS), as well as complex cytogenetic aberrations, and also with the development of secondary MDS and acute leukemia (AML) after chemotherapy. However, the incidence of TGC mutations in de novo MDS remains largely unknown. Recurrent somatic mutations in genes involving epigenetic, spliceosome, cell signaling and proliferation pathways are common in MDS and have prognostic significance. Identifying specific associations between mutational patterns helps characterize disease biology and thereby improve the therapeutic strategies