TERT rs2736100 A>C SNP and JAK2 46/1 haplotype significantly contribute to the occurrence of JAK2 V617F and CALR mutated myeloproliferative neoplasms – a multicentric study on 529 patients. (7th April 2016)

• Record Type: Journal Article
• Authors: Trifa, Adrian P.; Bănescu, Claudia; Tevet, Mihaela; Bojan, Anca; Dima, Delia; Urian, Laura; Török‐Vistai, Tünde; Popov, Viola M.; Zdrenghea, Mihnea; Petrov, Ljubomir; Vasilache, Anca; Murat, Meilin; Georgescu, Daniela; Popescu, Mihaela; Pătrinoiu, Oana; Balea, Marius; Costache, Roxana; Coleș, Elena; Șaguna, Carmen; Berbec, Nicoleta; Vlădăreanu, Ana‐Maria; Mihăilă, Romeo G.; Bumbea, Horia; Cucuianu, Andrei; Popp, Radu A.
• Is Part Of: British journal of haematology. Volume 174:Number 2(2016)
• Page Start: 218
• Page End: 226
• Publication Date: 2016-04-07
• Subjects: myeloproliferative neoplasms -- genetic predisposition -- single nucleotide polymorphisms -- JAK2 46/1 haplotype -- TERT rs2736100; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.14041
• Languages: English
• ISSNs: 0007-1048

Abstract

Abstract : Polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF) represent typical myeloproliferative neoplasms (MPN), usually characterized by specific somatic driver mutations ( JAK2 V617F, CALR and MPL ). JAK2 46/1 haplotype and telomerase reverse transcriptase gene ( TERT ) rs2736100 A>C single nucleotide polymorphism (SNP) could represent a large fraction of the genetic predisposition seen in MPN. The rs10974944 C>G SNP, tagging the JAK2 46/1 haplotype, and the TERT rs2736100 A>C SNP were genotyped in 529 MPN patients with known JAK2 V617F, CALR and MPL status, and 433 controls. JAK2 46/1 haplotype strongly correlated to JAK2 V617F‐positive MPN and, to a lesser extent, CALR ‐positive MPN. The TERT rs2736100 A>C SNP strongly correlated to all MPN, regardless of the phenotype (PV, ET or PMF) and major molecular subtype ( JAK2 V617F‐ or CALR ‐positive). While both variants have a significant contribution, they have nuanced consequences, with JAK2 46/1 predisposing essentially to JAK2 V617F‐positive MPN, and TERT rs2736100 A>C having a more general, non‐specific effect on all MPN, regardless of phenotype or major molecular subtype.