González Vela, María del CarmenDerdak, SophiaBeltran, SergiGut, MartaGut, Ivo GlynneVaqué, José Pedro2018-06-152018-06-152017González-Vela MD, Curiel-Olmo S, Derdak S, Beltran S, Santibañez M, Martinez N et al. Shared Oncogenic Pathways Implicated in Both Virus-Positive and UV-Induced Merkel Cell Carcinomas. J Invest Dermatol. 2017 Jan;137(1):197-206. DOI: 10.1016/j.jid.2016.08.015. Epub 2016 Sep 10022-202Xhttp://hdl.handle.net/10230/34916Merkel cell carcinoma (MCC) is a highly malignant neuroendocrine tumor of the skin whose molecular pathogenesis is not completely understood, despite the role that Merkel cell polyomavirus can play in 55-90% of cases. To study potential mechanisms driving this disease in clinically characterized cases, we searched for somatic mutations using whole-exome sequencing, and extrapolated our findings to study functional biomarkers reporting on the activity of the mutated pathways. Confirming previous results, Merkel cell polyomavirus-negative tumors had higher mutational loads with UV signatures and more frequent mutations in TP53 and RB compared with their Merkel cell polyomavirus-positive counterparts. Despite important genetic differences, the two Merkel cell carcinoma etiologies both exhibited nuclear accumulation of oncogenic transcription factors such as NFAT or nuclear factor of activated T cells (NFAT), P-CREB, and P-STAT3, indicating commonly deregulated pathogenic mechanisms with the potential to serve as targets for therapy. A multivariable analysis identified phosphorylated CRE-binding protein as an independent survival factor with respect to clinical variables and Merkel cell polyomavirus status in our cohort of Merkel cell carcinoma patients.application/pdfeng© 2016 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).info:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.jid.2016.08.015CarcinogenesisGene expression regulationMerkel cell carcinomaSkin neoplasmsTumor suppressor protein p53Tumor virus infectionsinfo:eu-repo/semantics/openAccess