title: TERT promoter mutations in skin cancer: the effects of sun exposure and X-irradiation.
abstract: The reactivation or reexpression of telomerase (TERT) is a widespread feature of neoplasms. TERT promoter mutations were recently reported that were hypothesized to result from UV radiation. In this retrospective study, we assessed TERT promoter mutations in 196 cutaneous basal cell carcinomas (BCCs), including 102 tumors from X-irradiated patients, 94 tumors from patients never exposed to ionizing radiation treatment, and 116 melanomas. We sought to evaluate the effects of UV and X-ray irradiation on TERT mutation frequency. TERT mutations were detected in 27% of BCCs from X-irradiated patients, 51% of BCCs from nonirradiated patients, and 22% of melanoma patients. TERT mutations were significantly increased in non-X-irradiated BCC patients compared with X-irradiated BCC patients; the mutations also presented a different mutation signature. In nonirradiated patients, TERT mutations were more frequent in BCCs of sun-exposed skin, supporting a possible causative role of UV radiation. In melanoma, TERT promoter mutations were generally restricted to intermittent sun-exposed areas and were associated with nodular and superficial spreading subtypes, increased thickness, ulceration, increased mitotic rate, and BRAFV600E mutations. Our results suggest that various carcinogenic factors may cause distinct TERT promoter mutations in BCC and that TERT promoter mutations might be associated with a poorer prognosis in melanoma.
authors.affiliation: Department of Cancer Biology, Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal.
authors.forename: Helena
authors.initials: H
authors.lastname: Pópulo
authors.affiliation: Department of Cancer Biology, Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Boaventura
authors.affiliation: Department of Cancer Biology, Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal; Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Vinagre
authors.affiliation: Department of Cancer Biology, Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Batista
authors.affiliation: Department of Cancer Biology, Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal.
authors.forename: Adélia
authors.initials: A
authors.lastname: Mendes
authors.affiliation: Department of Pathology and Oncology, Medical Faculty, University of Porto, Porto, Portugal.
authors.forename: Regina
authors.initials: R
authors.lastname: Caldas
authors.affiliation: Department of Pathology, Hospital S. João, Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Pardal
authors.affiliation: Department of Dermatology, Hospital São João, Porto, Portugal.
authors.forename: Filomena
authors.initials: F
authors.lastname: Azevedo
authors.affiliation: Department of Pathology, Hospital Pedro Hispano, Senhora da Hora, Portugal.
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Honavar
authors.affiliation: Department of Plastic Surgery, Hospital Pedro Hispano, Senhora da Hora, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Guimarães
authors.affiliation: Department of Cancer Biology, Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal; Department of Pathology and Oncology, Medical Faculty, University of Porto, Porto, Portugal; Department of Pathology, Hospital S. João, Porto, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Manuel Lopes
authors.affiliation: Department of Cancer Biology, Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal; Department of Pathology and Oncology, Medical Faculty, University of Porto, Porto, Portugal; Department of Pathology, Hospital S. João, Porto, Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sobrinho-Simões
authors.affiliation: Department of Cancer Biology, Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal; Department of Pathology and Oncology, Medical Faculty, University of Porto, Porto, Portugal. Electronic address: psoares@ipatimup.pt.
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
mesh_terms: D002280:Basal Cell Carcinoma / Q000235:genetics / Q000473:pathology; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000401:mortality / Q000473:pathology; D009154:Mutation; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D012878:Skin Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D013472:Sunlight / Q000009:adverse effects*; D019098:Telomerase / Q000235:genetics*; D014965:X-Rays / Q000009:adverse effects*
chemical_list: C509186:TERT protein, human; D019098:Telomerase