TERT positivity as a test for melanoma versus nevus had an accuracy of 87.3% [95% confidence interval (CI), 81.1-92.1], a sensitivity of 77.9% (95% CI, 68.9-85.4), a specificity of 98.6% (95% CI, 95.8-100), a positive predictive value of 98.5% (95% CI, 95.6-100), and a negative predictive value of 78.9% (95% CI, 72.6-85.4).
In this study, we investigated the impact of the subtypes of TERT mutations on disease-free and melanoma-specific survival in 287 patients with stage I/II nonacral melanoma.
Leukemia cell lines K-562, its vincristine-resistant derivative K-562-Lucena1 and daunorubicin-resistant derivative FEPS; gastric adenocarcinoma lines AGP01, ACP02 and ACP03; melanoma SK-Mel-103 cells; and MN01 and MRC5, two non-neoplastic cell lines were analyzed by real-time polymerase chain reaction in order to evaluate hTERT gene expression.
Assessing a single SNP located at TERT/CLPTM1L multi-cancer risk region as a genetic modifier for risk of pancreatic cancer and melanoma in Dutch CDKN2A mutation carriers.
Secondary genetic alterations overcome tumor suppressive mechanisms and allow the progression to intermediate lesions characterized by TERT-p mutation or to invasive melanomas displaying disruption of tumor suppressor genes.
TERT mutations were found in 68% of primary melanomas and 64% of metastases, and the mutation status was discordant between primary tumour and metastasis in 24% of the cases.
Two somatic mutations in the TERT promoter (C228T; C250T) have been identified as gain-of-function mutations that promote transcriptional activation of TERT in multiple cancers, such as melanoma and glioblastoma.
The mutation causes increased TERT and telomerase levels through creation of a binding motif for E-twenty six (ETS) transcription factors and the carriers develop melanoma with an early age of onset and rapid progression to metastasis.
Our data provides additional evidence that UV-induced <i>TERT</i> promoter mutation frequencies vary depending on melanoma subtype, but preserves its prognostic value.
The recent technological advances have allowed the identification of new genes involved in melanoma susceptibility: breast cancer 1 (BRCA1), BRCA1-associated protein 1 (BAP1), and telomerase reverse transcriptase (TERT).Tests on these genes allow to identify a larger number of high-risk individuals with a potential of developing familial melanoma and primary multiple melanomas.
To elucidate this question, ETS1 and TERT immunohistochemistry were performed on a panel of benign (n=27) and dysplastic nevi (n=34), radial growth phase (n=29), vertical growth phase (n=25) and metastatic melanomas (n=27).
Here, we show that frequently recurring promoter mutations in melanoma occur almost exclusively at cytosines flanked by a distinct sequence signature, TTCCG, with TERT as a notable exception.
A more exhaustive understanding of the different molecular mechanisms leading to increased TERT expression may guide development of prognostic assays to stratify AYA melanoma patients according to clinical risk.
Our study replicates 20 of 21 previously known melanoma-loci and confirms the association of the telomerase reverse transcriptase, TERT, with melanoma susceptibility at genome-wide significance.
Two recurrent point mutations in the promoter region of telomerase reverse transcriptase (TERT)--the key subunit of telomerase--have recently been identified in melanoma as well as a small sample of bladder cancer cell lines.
We investigated the regulation of TERT expression in melanoma cell lines and our results show that promoter mutations render TERT expression dependent on MAPK activation due to oncogenic BRAF or NRAS mutations.
The recent identification of a high frequency of driver mutations in the promoter of the telomerase reverse transcriptase (TERT) gene in cutaneous melanoma led us to investigate whether these mutations also occur in SNMM.
We observed statistically significant associations with melanoma for two lung cancer SNPs in the TERT-CLPTM1L locus (Bonferroni-corrected p<2.8x10-4), replicating known pleiotropic effects at this locus.