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Mutations in idiopathic cytopenia of undetermined significance assist diagnostics and correlate to dysplastic changes
Author(s) -
Hansen Jakob Werner,
Westman Maj Karoline,
Sjö Lene Dissing,
Saft Leonie,
Kristensen Lasse Sommer,
Ørskov Andreas Due,
Treppendahl Marianne,
Andersen Mette Klarskov,
Grønbæk Kirsten
Publication year - 2016
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.24554
Subject(s) - cytopenia , medicine , neuroblastoma ras viral oncogene homolog , mutation , gene mutation , population , oncology , etiology , hematopathology , pathology , bone marrow , cytogenetics , genetics , gene , cancer , biology , chromosome , colorectal cancer , environmental health , kras
Cytopenia is common in the elderly population and etiology may be difficult to assess. Here, we investigated the occurrence of mutations in patients with idiopathic cytopenia of undetermined significance and the usefulness in improving diagnostics. We included 60 patients with persistent cytopenia > 6 months without definite diagnosis of hematological neoplasm after routine assessment. Bone marrow material underwent a blinded morphology review and DNA was sequenced with a targeted 20 gene panel representing the most commonly mutated genes in myelodysplastic syndrome. Thirty seven (62%) patients carried at least one mutation at inclusion, and of these 95% carried a mutation in TET2 , ASXL1 , SRSF2, or DNMT3A . The most commonly mutated gene was TET2 observed in 43% of all patients. During one to eight years follow‐up seven patients progressed to a myeloid neoplasm and six of these had a detectable mutation at study entry. Median time to progression was 53 months (range 10–78), and at time of progression each patient had at least two mutations detected. Mutations in TP53 and NRAS were not present in patients at inclusion, but identified as secondary hits triggering progression. The morphology review was concordant in 68% of all cases, and 93% of the cases reclassified into the group “highly suspicious for MDS” had a mutation. All patients who had a concordant review “highly suspicious for MDS” had at least two mutations detected. Overall, we show that morphology examination is challenging in this heterogeneous group and targeted sequencing helps identify patients at risk of progression. Am. J. Hematol. 91:1234–1238, 2016. © 2016 Wiley Periodicals, Inc.