Open AccessHigh mutation burden in the checkpoint and micro-RNA processing genes in myelodysplastic syndrome
Author(s) -
Ivan S. Moiseev,
Nikolai Tsvetkov,
Ildar Barkhatov,
Maria V. Barabanshikova,
Dmitrii S. Bug,
Natalya Vitalievna Petuhova,
Артем Тишков,
Evgeny Bakin,
Е. А. Измайлова,
Alena I. Shakirova,
Alexander Kulagin,
Elena Morozova
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0248430
Subject(s) - gene , biology , mutation , genetics , myelodysplastic syndromes , ezh2 , drosha , cancer research , rna , rna interference , methylation , bone marrow , immunology
A number of sequencing studies identified the prognostic impact of somatic mutations in myelodysplastic syndrome (MDS). However the majority of them focused on methylation regulation, apoptosis and proliferation genes. Despite the number of experimental studies published on the role of micro-RNA processing and checkpoint genes in the development of MDS, the clinical data about mutational landscape in these genes is limited. We performed a pilot study which evaluated mutational burden in these genes and their association with common MDS mutations. High prevalence of mutations was observed in the genes studied: 54% had mutations in DICER1, 46% had mutations in LAG3, 20% in CTLA4, 23% in B7-H3, 17% in DROSHA, 14% in PD-1 and 3% in PD-1L. Cluster analysis that included these mutations along with mutations in ASXL1, DNMT3A, EZH2, IDH1, RUNX1, SF3B1, SRSF2, TET2 and TP53 effectively predicted overall survival in the study group (HR 4.2, 95%CI 1.3–13.6, p = 0.016). The study results create the rational for incorporating micro-RNA processing and checkpoint genes in the sequencing panels for MDS and evaluate their role in the multicenter studies.