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Application of an NGS ‐based 28‐gene panel in myeloproliferative neoplasms reveals distinct mutation patterns in essential thrombocythaemia, primary myelofibrosis and polycythaemia vera
Author(s) -
Delic Sabit,
Rose Dominic,
Kern Wolfgang,
Nadarajah Niroshan,
Haferlach Claudia,
Haferlach Torsten,
Meggendorfer Manja
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.14269
Subject(s) - myelofibrosis , polycythaemia , gene , mutation , genetics , essential thrombocythemia , myeloproliferative neoplasm , polycythemia vera , biology , cancer research , medicine , immunology , bone marrow
Molecular routine diagnostics for BCR ‐ ABL 1 ‐negative myeloproliferative neoplasms ( MPN ) currently focusses on mutations in JAK 2 , CALR and MPL . In recent years, recurrent mutations in MPN s have been identified in several other genes. We here present the validation of a next generation sequencing ( NGS )‐based 28‐gene panel and its use in MPN . We analysed the mutation status of 28 genes in 100 MPN patients [40 essential thrombocythaemia ( ET ), 30 primary myelofibrosis ( PMF ), 30 polycythaemia vera ( PV )] and found two or more mutated genes in 53 patients. Moreover, significantly more mutated splicing genes ( SF 3B1 , SRSF 2 and U2 AF 1) were present in PMF (0·60 mutated genes/patient) compared to ET (0·15) while no mutations in splicing genes were found in PV . Additionally, chromatin modification genes ( ASXL 1 and EZH 2 ) were frequently mutated in PMF patients (0·50) and, to a significantly lesser extent, in ET (0·13) and PV (0·07). Contrarily, DNA methylation genes ( DNMT 3A, IDH 1, IDH 2 and TET 2 ) were mutated most often in PV (0·5) and less frequently in ET (0·23) and PMF (0·20), but without reaching statistical significance. Our results demonstrate the feasibility and utility of NGS ‐based panel diagnostics for MPN . With 53% of the patients bearing two or more mutated genes, their prognostic relevance needs further studies.