Common germline variation at the TERT locus contributes to familial clustering of myeloproliferative neoplasms

Roland Jäger, Ashot S. Harutyunyan, Elisa Rumi, Daniela Pietra, Tiina Berg, Damla Olcaydu, Richard S. Houlston, Mario Cazzola, Robert Kralovics

Research output: Contribution to journalArticlepeer-review

Abstract

The C allele of the rs2736100 single nucleotide polymorphism located in the second intron of the TERT gene has recently been identified as a susceptibility factor for myeloproliferative neoplasms (MPN) in the Icelandic population. Here, we evaluate the role of TERT rs2736100_C in sporadic and familial MPN in the context of the previously identified JAK2 GGCC predisposition haplotype. We have confirmed the TERT rs2736100_C association in a large cohort of Italian sporadic MPN patients. The risk conferred by TERT rs2736100_C is present in all molecular and diagnostic MPN subtypes. TERT rs2736100_C and JAK2 GGCC are independently predisposing to MPN and have an additive effect on disease risk, together explaining a large fraction of the population attributable fraction (PAF=73.06%). We found TERT rs2736100_C significantly enriched (P=0.0090) in familial MPN compared to sporadic MPN, suggesting that low-penetrance variants may be responsible for a substantial part of familial clustering in MPN.

Original languageEnglish
Pages (from-to)1107-1110
Number of pages4
JournalAmerican Journal of Hematology
Volume89
Issue number12
DOIs
Publication statusPublished - Dec 1 2014

ASJC Scopus subject areas

  • Hematology

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