Genome wide DNA methylation profiling identifies specific epigenetic features in high-risk cutaneous squamous cell carcinoma


Autoři: David Hervás-Marín aff001;  Faatiemah Higgins aff002;  Onofre Sanmartín aff004;  Jose Antonio López-Guerrero aff006;  M. Carmen Bañó aff002;  J. Carlos Igual aff002;  Inma Quilis aff002;  Juan Sandoval aff007
Působiště autorů: Department of Biostatistics, Instituto de Investigación Sanitaria La Fe, Valencia, Spain aff001;  Estructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (ERI BIOTECMED) Universitat de València, Burjassot, Valencia, Spain aff002;  Departament de Bioquímica i Biologia Molecular, Universitat de València, Burjassot, Valencia, Spain aff003;  Dermatology Department, Instituto Valenciano de Oncología, Valencia, Spain aff004;  Facultad de Medicina, Universidad Católica de Valencia, Valencia, Spain aff005;  Laboratory of Molecular Biology, Instituto Valenciano de Oncología, Valencia, Spain aff006;  Biomarkers and Precision Medicine Unit (UByMP), Instituto de Investigación Sanitaria La Fe, Valencia, Spain aff007
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223341

Souhrn

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. Although most cSCCs have good prognosis, a subgroup of high-risk cSCC has a higher frequency of recurrence and mortality. Therefore, the identification of molecular risk factors associated with this aggressive subtype is of major interest. In this work we carried out a global-scale approach to investigate the DNA-methylation profile in patients at different stages, from premalignant actinic keratosis to low-risk invasive and high-risk non-metastatic and metastatic cSCC. The results showed massive non-sequential changes in DNA-methylome and identified a minimal methylation signature that discriminates between stages. Importantly, a direct comparison of low-risk and high-risk stages revealed epigenetic traits characteristic of high-risk tumours. Finally, a prognostic prediction model in cSCC patients identified a methylation signature able to predict the overall survival of patients. Thus, the analysis of DNA-methylation in cSCC revealed changes during the evolution of the disease through the different stages that can be of great value not only in the diagnosis but also in the prognosis of the disease.

Klíčová slova:

Cancer detection and diagnosis – Carcinomas – DNA methylation – Epigenetics – Prognosis – Squamous cell carcinomas – Treatment guidelines – Actinic keratosis


Zdroje

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Článek vyšel v časopise

PLOS One


2019 Číslo 12