Assessment of Telomere Length and Molecular Characterization of TERT Gene Promoter in Periampullary Carcinomas

Abstract

Genetic and epigenetic alterations of the telomere maintenance machinery like telomere length and telomerase reverse transcriptase (encoded by TERT gene) are reported in several human malignancies. However, there is limited knowledge on the status of the telomere machinery in periampullary carcinomas (PAC) that are rare and heterogeneous groups of cancers arising from different anatomic sites around the ampulla of Vater. In the current study, we investigated the relative telomere length (RTL) and the most frequent genetic and epigenetic alterations in the TERT promoter in PAC (n=20) and compared with tumor-adjacent nonpathological duodenum (NDu; n=16). We found shorter RTLs (1.27 vs 1.33, P=0.01) and lower TERT protein expression (p=0.04) in PAC tissues as compared to the NDu. Although we did not find any mutation at two reactivating hotspot mutation sites of the TERT promoter, we detected polymorphism in 55% (11/20) of the cases at rs2853669 (T>C). Also, we found a hypermethylated region in the TERT promoter of PACs consisting of four CpGs (cg10896616 with ∆β 7%; cg02545192 with ∆β 9%; cg03323598 with ∆β 19%; and cg07285213 with ∆β 15%). In conclusion, we identified shorter telomeres with DNA hypermethylation in the TERT promoter region and lower TERT protein expression in PAC tissues. Further studies with a larger sample size are necessary to substantiate these results.