Open AccessGenome wide DNA methylation profiling identifies specific epigenetic features in high-risk cutaneous squamous cell carcinoma
Author(s) -
David HervásMarín,
Faatiemah Higgins,
O. Sanmartín,
José Antonio LöpezGuerrero,
M. Carmen Bañó,
J. Carlos Igual,
Inma Quilis,
Juan Sandoval
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0223341
Subject(s) - dna methylation , epigenetics , methylation , biology , oncology , skin cancer , bioinformatics , medicine , cancer research , cancer , genetics , gene , gene expression
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.