TERT Promoter Mutations in Skin Cancer: The Effects of Sun Exposure and X-Irradiation

A team of IPATIMUP researchers had previously demonstrated that alterations in the telomerase gene are common to different types of cancer, including tumors of the skin, brain, bladder, and thyroid and are associated with increased levels of this enzyme in tumors. The same team now published a study in Journal of Investigative Dermatology, where they analyzed two types of skin cancer, melanoma and basal cell carcinoma, and demonstrates that telomerase gene mutations are associated with sun exposure and are also associated with a poorer prognosis in melanoma.

Autores e afiliações:

Helena Pópulo^1,*, Paula Boaventura^1,*, João Vinagre^1,2,*, Rui Batista¹, Adélia Mendes¹, Regina Caldas³, Joana Pardal⁴, Filomena Azevedo⁵, Mrinalini Honavar⁶, Isabel Guimarães⁶, José Manuel Lopes^1,3,4, Manuel Sobrinho-Simões^1,3,4, Paula Soares^1,3,#.

1- Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), 4200-465 Porto, Portugal

2- Institute of Biomedical Sciences Abel Salazar, University of Porto, 4050-313 Porto, Portugal

3- Department of Pathology and Oncology, Medical Faculty, University of Porto, 4200 - 319 Porto, Portugal

4- Department of Pathology, Hospital S. João, 4200 - 319 Porto, Portugal

5- Department of Dermatology, Hospital São João, 4200-465 Porto, Portugal.

6- Hospital Pedro Hispano, 4464-513 Senhora da Hora, Portugal.

*- These authors contributed equally.

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.

Revista:

Journal of Investigative Dermatology

Link:

http://www.nature.com/jid/journal/vaop/ncurrent/full/jid2014163a.html