title: Telomerase reverse transcriptase (TERT) promoter mutations in Korean melanoma patients.
abstract: Telomerase reverse transcriptase (TERT) is the reverse transcriptase component of the telomeric complex, which synthesizes terminal DNA to protect chromosomal ends and to maintain genomic integrity. In melanoma, mutation inTERTpromoter region is a common event and theses promoter variants have been shown to be associated with increased gene expression, decreased telomere length and poorer outcome. In this study, we determined the frequency ofTERTpromoter mutation in 88 Korean primary melanoma patients and aimed to see the association ofTERTpromoter mutation status to other major molecular features, such asBRAF,NRAS,KITmutations and correlate with clinicopathological features. In our study, acral melanoma (n=46, 52.3%) was the most common type. Overall,TERTpromoter mutation was observed in 15 cases (17%) with ten c. -124C>T altertions and five c. -146C>T alterations. None of our samples showed CC>TT mutation which is considered pathognomonic of UV induction. Among the 46 acral melanoma patients, 5 patients (10.9%) harboredTERTpromoter mutation. Tumors withTERTpromoter mutation showed significantly greater Breslow thickness compared to WT tumors (P=0.039). A combined analysis for the presence ofTERTpromoter andBRAFmutations showed that patients with bothTERTpromoter andBRAFmutation showed decreased survival compared with those with onlyTERTpromoter mutation, onlyBRAFmutation, or without mutations in eitherTERTpromoter orBRAF(P=0.035). Our data provides additional evidence that UV-inducedTERTpromoter mutation frequencies vary depending on melanoma subtype, but preserves its prognostic value.
authors.affiliation: Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical SchoolBoston, MA, USA; Department of Dermatology, Cutaneous Biology Research Institute, Yonsei University College of MedicineSeoul, Korea.
authors.forename: Mi Ryung
authors.initials: MR
authors.lastname: Roh
authors.affiliation: Songdang Institute for Cancer Research, Yonsei Cancer Center, Yonsei University College of Medicine Seoul, Korea.
authors.forename: Kyu-Hyun
authors.initials: KH
authors.lastname: Park
authors.affiliation: Department of Dermatology, Cutaneous Biology Research Institute, Yonsei University College of Medicine Seoul, Korea.
authors.forename: Kee Yang
authors.initials: KY
authors.lastname: Chung
authors.affiliation: Songdang Institute for Cancer Research, Yonsei Cancer Center, Yonsei University College of MedicineSeoul, Korea; Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of MedicineSeoul, Korea.
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Songdang Institute for Cancer Research, Yonsei Cancer Center, Yonsei University College of MedicineSeoul, Korea; Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of MedicineSeoul, Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.affiliation: Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School Boston, MA, USA.
authors.forename: Hensin
authors.initials: H
authors.lastname: Tsao
keywords: Korean; TERT mutation; melanoma; prognosis; survival