title: 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.
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.
authors.affiliation: Department of Medical Genetics, 'Iuliu Hațieganu' University of Medicine and Pharmacy, Cluj-Napoca, Romania.|Department of Genetics, 'Ion Chiricuță' Cancer Institute, Cluj-Napoca, Romania.
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Trifa
authors.affiliation: Department of Genetics, University of Medicine and Pharmacy, Tîrgu-Mureș, Romania.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bănescu
authors.affiliation: Department of Haematology, Colentina Hospital, Bucharest, Romania.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Tevet
authors.affiliation: Department of Haematology, 'Ion Chiricuță' Cancer Institute, Cluj-Napoca, Romania.|Department of Haematology, 'Iuliu Hațieganu' University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Anca
authors.initials: A
authors.lastname: Bojan
authors.affiliation: Department of Haematology, 'Ion Chiricuță' Cancer Institute, Cluj-Napoca, Romania.
authors.forename: Delia
authors.initials: D
authors.lastname: Dima
authors.affiliation: Department of Haematology, 'Ion Chiricuță' Cancer Institute, Cluj-Napoca, Romania.|Department of Haematology, 'Iuliu Hațieganu' University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Laura
authors.initials: L
authors.lastname: Urian
authors.affiliation: Department of Haematology, 'Ion Chiricuță' Cancer Institute, Cluj-Napoca, Romania.|Department of Haematology, 'Iuliu Hațieganu' University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Tünde
authors.initials: T
authors.lastname: Török-Vistai
authors.affiliation: Department of Haematology, Colentina Hospital, Bucharest, Romania.
authors.forename: Viola M
authors.initials: VM
authors.lastname: Popov
authors.affiliation: Department of Haematology, 'Ion Chiricuță' Cancer Institute, Cluj-Napoca, Romania.|Department of Haematology, 'Iuliu Hațieganu' University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Mihnea
authors.initials: M
authors.lastname: Zdrenghea
authors.affiliation: Department of Haematology, 'Ion Chiricuță' Cancer Institute, Cluj-Napoca, Romania.|Department of Haematology, 'Iuliu Hațieganu' University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Ljubomir
authors.initials: L
authors.lastname: Petrov
authors.affiliation: Department of Haematology, 'Ion Chiricuță' Cancer Institute, Cluj-Napoca, Romania.
authors.forename: Anca
authors.initials: A
authors.lastname: Vasilache
authors.affiliation: Department of Haematology, Colentina Hospital, Bucharest, Romania.
authors.forename: Meilin
authors.initials: M
authors.lastname: Murat
authors.affiliation: Department of Haematology, Colentina Hospital, Bucharest, Romania.
authors.forename: Daniela
authors.initials: D
authors.lastname: Georgescu
authors.affiliation: Department of Haematology, Colentina Hospital, Bucharest, Romania.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Popescu
authors.affiliation: Department of Haematology, Colentina Hospital, Bucharest, Romania.
authors.forename: Oana
authors.initials: O
authors.lastname: Pătrinoiu
authors.affiliation: Department of Haematology, Colentina Hospital, Bucharest, Romania.
authors.forename: Marius
authors.initials: M
authors.lastname: Balea
authors.affiliation: Department of Medical Genetics, 'Iuliu Hațieganu' University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Roxana
authors.initials: R
authors.lastname: Costache
authors.affiliation: Department of Haematology, Colțea Hospital, 'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Elena
authors.initials: E
authors.lastname: Coleș
authors.affiliation: Department of Haematology, Colțea Hospital, 'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Carmen
authors.initials: C
authors.lastname: Șaguna
authors.affiliation: Department of Haematology, Colțea Hospital, 'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Nicoleta
authors.initials: N
authors.lastname: Berbec
authors.affiliation: Department of Haematology, University Emergency Hospital, 'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Vlădăreanu
authors.affiliation: Department of Haematology, Sibiu County Emergency Hospital, 'Lucian Blaga' University, Sibiu, Romania.
authors.forename: Romeo G
authors.initials: RG
authors.lastname: Mihăilă
authors.affiliation: Department of Haematology, University Emergency Hospital, 'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Horia
authors.initials: H
authors.lastname: Bumbea
authors.affiliation: Department of Haematology, 'Ion Chiricuță' Cancer Institute, Cluj-Napoca, Romania.|Department of Haematology, 'Iuliu Hațieganu' University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Andrei
authors.initials: A
authors.lastname: Cucuianu
authors.affiliation: Department of Medical Genetics, 'Iuliu Hațieganu' University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Radu A
authors.initials: RA
authors.lastname: Popp
mesh_terms: D000328:Adult; D000368:Aged; D037282:Calreticulin / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics*; D010641:Phenotype; D011087:Polycythemia Vera / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D055728:Primary Myelofibrosis / Q000235:genetics; D019098:Telomerase / Q000235:genetics*; D013920:Thrombocythemia, Essential / Q000235:genetics; D055815:Young Adult
chemical_list: D037282:Calreticulin; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C509186:TERT protein, human; D019098:Telomerase
keywords: JAK2 46/1 haplotype; TERT rs2736100; genetic predisposition; myeloproliferative neoplasms; single nucleotide polymorphisms