Suppressor‐type TERT mutations associated with recurrence in ovarian clear cell carcinoma

Abstract

Several cancers harbor "enhancer-type" mutations of the telomerase reverse transcriptase (TERT) promoter for immortalization. Here, we report that 8.6% (8/93) of ovarian clear cell carcinomas (OCCCs) possess the "suppressor-type" TERT promoter mutation. The recurrence rate of OCCCs with "suppressor-type" TERT promoter mutations was 62.5% (5/8) and was significantly higher than that of the "unaffected-type" with no mutation (20.8%, 15/72) or "enhancer-type" TERT promoter mutations (7.7%, 1/13). Our findings show that the acquired suppression of TERT is closely associated with OCCC development and recurrence, indicating the need for further research on telomerase suppression in cancers. K E Y W O R D S"enhancer-type" TERT promoter mutation, "suppressor-type" TERT promoter mutation, ovarian cancer, ovarian clear cell carcinoma, recurrence, telomerase reverse transcriptase, telomere

The -124C>T mutation of TERT promoter indicated a favorable prognosis in OCCC: a monoinstitutional study in China

“…(Yoo H, 2023) A similar conclusion from Irshaid et al reported that a TERTp mutation could be further strati ed as high-risk OCCC in the no speci c molecular pro le subgroup (Irshaid, Costigan et al, 2023). In contrast to the above research, Kobayashi et al reported that the progression-free survival rate of the "enhancer-type" group including the hotspot mutations of TERTp was signi cantly longer than that of the wild-type and "suppressor-type" (with uncommon mutations) mutation groups (Kobayashi et al, 2023). While no signi cant difference in disease-speci c overall survival was observed between patients with and without TERTp hotspot mutations in the cohorts of Nishikimi et al and Wu et al(Nishikimi et al, 2018, Wu et al, 2014 In our study, patients with the − 124C > T mutation had longer PFS and OS than those with wild-type.…”

“…Ayhan et al, 2014) Another study reported that the TERTp hotspot mutations (-124C > T and − 146C > T) had a higher promoter activity than the wild-type, and the promoter activity of the uncommon site mutations was the lowest (Kobayashi, Nishikimi et al, 2023). Furthermore, TERT expression increased with tumor grade and stage (Maraei, Hatta et al, 2012).…”