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) which 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 and compared it with tumor-adjacent nonpathological duodenum (NDu). 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 45% (9/20) 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 Δβ 7%; cg02545192 with Δβ 9%; cg03323598 with Δβ 19%; and cg07285213 with Δβ 15%). In conclusion, we identified shorter telomeres with DNA hypermethylation in the TERT promoter region and lower TERT protein expression in PAC tissues. These results could be used further to investigate molecular pathology and develop theranostics for PAC.

Departamento de Genética Programa de Pós graduação em Genética e Biologia Molecular Universidade Federal do Rio Grande do Sul Porto Alegre Rio Grande do Sul Brazil

Departamento de Patologia Faculdade de Medicina Universidade Federal do Rio Grande do Sul Porto Alegre Rio Grande do Sul Brazil

Department of Anatomy Histology and Embryology School of Medicine University of Split Split Croatia

Department of Pathology University Hospital of Split Split Croatia

Faculty of Science Charles University Prague Czech Republic

Grupo de Vias Biliares e Pâncreas Cirurgia do Aparelho Digestivo Hospital de Clínicas de Porto Alegre Porto Alegre Rio Grande do Sul Brazil

International Agency for Research on Cancer Lyon France

Laboratório de Medicina Genômica Centro de Pesquisa Experimental Hospital de Clínicas de Porto Alegre Porto Alegre Rio Grande do Sul Brazil

Programa de Pós graduação em Medicina Ciências Cirúrgicas Universidade Federal do Rio Grande do Sul Porto Alegre Rio Grande do Sul Brazil

Serviço de Patologia Hospital de Clínicas de Porto Alegre Porto Alegre Rio Grande do Sul Brazil

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