Frequency of TERT promoter mutations in human cancers

Abstract

Reactivation of telomerase has been implicated in human tumorigenesis, but the underlying mechanisms remain poorly understood. Here we report the presence of recurrent somatic mutations in the TERT promoter in cancers of the central nervous system (43%), bladder (59%), thyroid (follicular cell-derived, 10%) and skin (melanoma, 29%). In thyroid cancers, the presence of TERT promoter mutations (when occurring together with BRAF mutations) is significantly associated with higher TERT mRNA expression, and in glioblastoma we find a trend for increased telomerase expression in cases harbouring TERT promoter mutations. Both in thyroid cancers and glioblastoma, TERT promoter mutations are significantly associated with older age of the patients. Our results show that TERT promoter mutations are relatively frequent in specific types of human cancers, where they lead to enhanced expression of telomerase.

Telomerase reverse transcriptase mutations in plasma DNA in patients with hepatocellular carcinoma or cirrhosis: Prevalence and risk factors

“…TERT promoter mutations are relatively frequent in human cancers characterized by low rates of self‐renewal, such as gliomas, bladder cancers, and melanoma,13, 14 and have been identified as recurrent somatic mutation in regulatory regions of human cancer genomes 15. The aims of this study were 2‐fold: (1) to determine whether TERT promoter mutations could be detected in plasma cfDNA in patients with HCC but also in patients with cirrhosis at risk for HCC; and (2) to characterize patients with HCC or cirrhosis with high frequency of TERT promoter mutations.…”

Hotspot TERT promoter mutations are rare events in testicular germ cell tumors

“…Recent studies have described a high frequency of TERT promoter mutation in several human tumors and human cell lines [2-5, 21, 22]. In glioblastomas and papillary thyroid cancer, the mutations were associated with older age at diagnosis [3]. Another recent study demonstrated association Mixed tumor 9 − SX I n/a n/a n/a Alive 4 c.-146:C>T TT 43 Seminoma 6.5 + S1 I n/a n/a n/a Alive n/a not applicable a Vascular invasion between TERT promoter mutations and older patient age, larger tumor size, distant metastases, and shorter disease specific survival in papillary thyroid cancer [23].…”

“…In our study, we identified TERT promoter mutations in small number of cases that exhibited different stages, invasiveness, and histologies, hindering meaningful statistical associations. The TERT mutation profile has been associated with other molecular features in several tumor types, in particular an interesting association with BRAF mutation in skin melanomas and thyroid cancer [3,4]. The frequency and clinical impact of BRAF mutations in TGCT is still controversial [25,26].…”

“…The analysis of hotspot mutations of TERT promoter regions was performed by PCR followed by direct Sanger sequencing as described previously by our group [3,18,19].…”

“…One of the key human cancer hallmarks is the abnormal upregulation of telomerase, that is codified by the telomerase reverse transcriptase (TERT) gene [1]. Recent studies identified the presence of hotspot somatic mutations in the promoter region of TERT gene, specifically the −124:C>T and −146:C>T mutations, in a range of human cancers such as bladder, gliomas, thyroid and melanoma [2][3][4][5]. These mutations have been shown to create a new binding motif sites for ETS transcription factors, which induces upregulation of TERT levels [2,5,6].…”