Naslov
Telomere length assessment and molecular characterization of TERT gene promoter in periampullary carcinomas

Autori
Gregório, Cleandra ; ... ; Vukojević, Katarina ; Glavina Durdov, Merica ; ... ; Herceg, Zdenko ; Talukdar, Fazlur Rahman

Izvornik
Gene (0378-1119) 873 (2023); 14760, 10

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Periampullary carcinomaTERT expressionTERT promoter, Relative Telomere LengthTelomeraseTelomeres

Sažetak
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 Deltabeta 7% ; cg02545192 with Deltabeta 9% ; cg03323598 with Deltabeta 19% ; and cg07285213 with Deltabeta 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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA