RT Journal Article SR Electronic T1 Genome wide DNA methylation profiling identifies specific epigenetic features in high-risk cutaneous squamous cell carcinoma JF bioRxiv FD Cold Spring Harbor Laboratory SP 777227 DO 10.1101/777227 A1 David Hervás-Marín A1 Faatiemah Higgins A1 Onofre Sanmartín A1 Jose Antonio López-Guerrero A1 M. Carmen Bañó A1 J. Carlos Igual A1 Inma Quilis A1 Juan Sandoval YR 2019 UL http://biorxiv.org/content/early/2019/09/20/777227.abstract AB 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.