High mutation burden in the checkpoint and micro-RNA processing genes in myelodysplastic syndrome.

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 pro...

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Main Authors: Ivan Sergeevich Moiseev, Nikolay Yurevich Tcvetkov, Ildar Munerovich Barkhatov, Maria Vladimirovna Barabanshikova, Dmitrii Sergeevich Bug, Natalya Vitalievna Petuhova, Artem Valerievich Tishkov, Evgenyi Alexandrovich Bakin, Ekaterina Andreevna Izmailova, Alena Igorevna Shakirova, Alexandr Dmitrievich Kulagin, Elena Vladislavovna Morozova
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0248430&type=printable
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author Ivan Sergeevich Moiseev
Nikolay Yurevich Tcvetkov
Ildar Munerovich Barkhatov
Maria Vladimirovna Barabanshikova
Dmitrii Sergeevich Bug
Natalya Vitalievna Petuhova
Artem Valerievich Tishkov
Evgenyi Alexandrovich Bakin
Ekaterina Andreevna Izmailova
Alena Igorevna Shakirova
Alexandr Dmitrievich Kulagin
Elena Vladislavovna Morozova
author_facet Ivan Sergeevich Moiseev
Nikolay Yurevich Tcvetkov
Ildar Munerovich Barkhatov
Maria Vladimirovna Barabanshikova
Dmitrii Sergeevich Bug
Natalya Vitalievna Petuhova
Artem Valerievich Tishkov
Evgenyi Alexandrovich Bakin
Ekaterina Andreevna Izmailova
Alena Igorevna Shakirova
Alexandr Dmitrievich Kulagin
Elena Vladislavovna Morozova
author_sort Ivan Sergeevich Moiseev
collection DOAJ
description 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.
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spelling doaj-art-28e62eeb8eee4b4d81e100826feb3c572025-08-20T02:00:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01163e024843010.1371/journal.pone.0248430High mutation burden in the checkpoint and micro-RNA processing genes in myelodysplastic syndrome.Ivan Sergeevich MoiseevNikolay Yurevich TcvetkovIldar Munerovich BarkhatovMaria Vladimirovna BarabanshikovaDmitrii Sergeevich BugNatalya Vitalievna PetuhovaArtem Valerievich TishkovEvgenyi Alexandrovich BakinEkaterina Andreevna IzmailovaAlena Igorevna ShakirovaAlexandr Dmitrievich KulaginElena Vladislavovna MorozovaA 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0248430&type=printable
spellingShingle Ivan Sergeevich Moiseev
Nikolay Yurevich Tcvetkov
Ildar Munerovich Barkhatov
Maria Vladimirovna Barabanshikova
Dmitrii Sergeevich Bug
Natalya Vitalievna Petuhova
Artem Valerievich Tishkov
Evgenyi Alexandrovich Bakin
Ekaterina Andreevna Izmailova
Alena Igorevna Shakirova
Alexandr Dmitrievich Kulagin
Elena Vladislavovna Morozova
High mutation burden in the checkpoint and micro-RNA processing genes in myelodysplastic syndrome.
PLoS ONE
title High mutation burden in the checkpoint and micro-RNA processing genes in myelodysplastic syndrome.
title_full High mutation burden in the checkpoint and micro-RNA processing genes in myelodysplastic syndrome.
title_fullStr High mutation burden in the checkpoint and micro-RNA processing genes in myelodysplastic syndrome.
title_full_unstemmed High mutation burden in the checkpoint and micro-RNA processing genes in myelodysplastic syndrome.
title_short High mutation burden in the checkpoint and micro-RNA processing genes in myelodysplastic syndrome.
title_sort high mutation burden in the checkpoint and micro rna processing genes in myelodysplastic syndrome
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0248430&type=printable
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