The germline sequence variant rs2736100_C in TERT associates with myeloproliferative neoplasms

Co-occurrence of Myeloproliferative Neoplasms and Solid Tumors Is Attributed to a Synergism Between Cytoreductive Therapy and the Common TERT Polymorphism rs2736100

“…In the CALR þ subgroup, a single allele of JAK2 haplotype exerted a similar effect to that of JAK2 haplotype homozygosity (Table 2). Similarly to previous reports (4,5), in the Hungarian population the PAF for TERT rs2736100_C was larger (52.5%), than the PAF for JAK2 rs12343867_C (46.0%). Combined PAF for both common variants (74.4%) was estimated to explain the genetic background of the majority of our sporadic MPN.…”

“…Our results are in line with earlier observations that TERT and JAK2 risk alleles have independent and additive impact on MPN predisposition suggesting different underlying pathomechanisms in the background of MPN susceptibility owing to TERT and JAK2 variants. We also investigated CML and AML cases to further explore the potential role of TERT variant in the development of other myeloid neoplasms, and we observed no association of TERT rs2736100_C allele with CML or AML susceptibility, similarly to the findings by Oddsson and colleagues (5). On the other hand, AML has a heterogeneous genetic, etiologic background, and we cannot exclude associations of TERT variant allele with distinct AML subtypes (e.g., AML with complex karyotype).…”

“…lung, bladder; ref. 3) and recently for sporadic and familial MPN (4)(5)(6). The TERT gene encodes the catalytic subunit of telomerase, which is essential for the maintenance of telomere length.…”

Molecular determinants of pathogenesis and clinical phenotype in myeloproliferative neoplasms

“…A number of more common, but lower penetrance germline variants have been associated with MPN development, including single nucleotide polymorphisms (SNPs) present in, or close to, telomerase reverse transcriptase (TERT) 86 and "MDS1 and EVI1 complex locus" (MECOM). 87 Two JAK2 haplotypes (46 and 1) are found to be in linkage disequilibrium (with the exception of one SNP).…”

Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly

“…Previously, we reported an association between myeloproliferative neoplasms and a common variant in TERT (rs2736100, r 2 5 0.28 vs rs34002450). 46 Conditional analysis showed that the CH association mapped preferentially to rs34002450 (P adj 5 3.6 3 10…”