Mutações do promotor do gene TERT em cancro da pele: o efeito da exposição solar e radiação X

Uma equipa de investigadores do IPATIMUP tinha anteriormente demonstrado que alterações no gene da Telomerase são comuns a diferentes tipos de cancro, incluindo tumores da pele, do cérebro, da bexiga e da tiróide e estão associadas ao aumento dos níveis desta enzima nos tumores. A mesma equipa publicou agora um estudo na revista Journal of Investigative Dermatology, onde analisou dois tipos de cancro de pele, melanomas e carcinomas basocelulares, e demonstra que as mutações no gene da Telomerase se associam a exposição solar. E em melanoma estas mutações encontram-se também associadas ao pior prognóstico dos pacientes.

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