title: Telomerase reverse transcriptase promoter mutations in primary cutaneous melanoma.
abstract: We previously reported a disease segregating causal germline mutation in a melanoma family and recurrent somatic mutations in metastasized tumours from unrelated patients in the core promoter region of the telomerase reverse transcriptase (TERT) gene. Here we show that the TERT promoter mutations, besides causing an increased gene expression, associate with increased patient age, increased Breslow thickness and tumour ulceration in 287 primary melanomas. The mutations are more frequent at both intermittently and chronically sun-exposed sites than non-exposed sites and tend to co-occur with BRAF and CDKN2A alterations. The association with parameters generally connected with poor outcome, coupled with high recurrence and mechanistic relevance, raises the possibility of the eventual use of TERT promoter mutations in the disease management.
authors.affiliation: 1] Division of Molecular Genetic Epidemiology, German Cancer Research Center, 69120 Heidelberg, Germany [2].
authors.forename: Barbara
authors.initials: B
authors.lastname: Heidenreich
authors.affiliation: 1] Department of Dermatology, Instituto Valenciano de Oncologia, Valencia 46009, Spain [2] Universidad Catolica de Valencia, Valencia 46001, Spain [3].
authors.forename: Eduardo
authors.initials: E
authors.lastname: Nagore
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, 69120 Heidelberg, Germany.
authors.forename: P Sivaramakrishna
authors.initials: PS
authors.lastname: Rachakonda
authors.affiliation: Laboratory of Molecular Biology, Instituto Valenciano de Oncologia, Valencia 46009, Spain.
authors.forename: Zaida
authors.initials: Z
authors.lastname: Garcia-Casado
authors.affiliation: Department of Dermatology, Instituto Valenciano de Oncologia, Valencia 46009, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Requena
authors.affiliation: Department of Pathology, Instituto Valenciano de Oncologia, Valencia 46009, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Traves
authors.affiliation: Department of General Dermatology, Medical University of Graz, Graz 8036, Austria.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Becker
authors.affiliation: Departement de Genetique, Hôpital Bichat-Claude Bernard, APHP, Paris 75877, France.
authors.forename: Nadem
authors.initials: N
authors.lastname: Soufir
authors.affiliation: 1] Division of Molecular Genetic Epidemiology, German Cancer Research Center, 69120 Heidelberg, Germany [2] Center for Primary Health Care Research, Lund University, Malmö, Lund 221 00, Sweden.
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, 69120 Heidelberg, Germany.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D013472:Sunlight; D019098:Telomerase / Q000235:genetics*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D019098:Telomerase