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Title

Shared oncogenic pathways implicated in both virus-positive and UV-induced merkel cell carcinomas

AuthorsGonzález-Vela, María del Carmen; Curiel-Olmo, Soraya; Agraz-Doblas, Antonio; Varela, Ignacio ; Piris, Miguel A.; Vaqué, José P.
Issue Date2017
PublisherElsevier
CitationJournal of Investigative Dermatology 137(1): 197-206 (2017)
AbstractMerkel 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.
DescriptionMdC González-Vela et al.
Publisher version (URL)https://doi.org/10.1016/j.jid.2016.08.015
URIhttp://hdl.handle.net/10261/164572
Identifiersdoi: 10.1016/j.jid.2016.08.015
e-issn: 1523-1747
issn: 0022-202X
Appears in Collections:(IBBTEC) Artículos
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