Publication Date:
2018-11-29
Description:
Introduction: MF is a Philadelphia-negative myeloproliferative neoplasm (Ph-negative MPN) associated with driver mutations in the JAK-STAT pathway (e.g. JAK2, CALR, MPL) and other mutations in genes that lead to epigenetic changes and altered RNA splicing (e.g. TET2, SRSF2, ASXL1, EZH2). The RAS-signaling pathway is frequently altered in acute myeloid leukemia (AML) and other myeloid malignancies, but few studies have evaluated the prevalence of such mutations in patients with MF. We sought to describe the frequency and clinical features of RAS mutations in patients with MF. Methods: We analyzed next-generation sequencing data from 723 patients with a diagnosis of primary MF (N=520), post-PV MF (N=119) and post-ET MF (N=84). Sequencing was performed with either paired tumor-normal whole exome sequencing (WES; N=56) or selected gene panel for genes associated with myeloid malignancies (N=667). The following 16 genes were analyzed in all 723 patients and were considered as the common denominator for analysis: ASXL1, CALR, DNMT3A, EZH2, FLT3, IDH1, IDH2, JAK2, KIT, KRAS, MPL, NRAS, RUNX1, TET2, TP53, WT1. RAS mutations were considered as oncogenic mutations in NRAS and/or KRAS. Molecular high risk (MHR) mutations were considered as mutations in any one of the 4 genes: ASXL1, EZH2, IDH1, IDH2 (SRSF2 mutations were not included since they were not evaluated in all cases). Odds ratio (OR) and P-values were estimated using Fisher's exact test in pairwise comparisons among genetic features, and P-values were adjusted for multiple comparisons using the Benjamini-Hochberg procedure, with significant Q-values considered as those
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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