Shared oncogenic pathways implicated in both virus-positive and UV-induced merkel cell carcinomas
Mostra el registre complet Registre parcial de l'ítem
- dc.contributor.author González Vela, María del Carmenca
- dc.contributor.author Derdak, Sophiaca
- dc.contributor.author Beltran, Sergica
- dc.contributor.author Gut, Martaca
- dc.contributor.author Gut, Ivo Glynneca
- dc.contributor.author Vaqué, José Pedroca
- dc.date.accessioned 2018-06-15T07:50:03Z
- dc.date.available 2018-06-15T07:50:03Z
- dc.date.issued 2017
- dc.description.abstract Merkel 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.
- dc.format.mimetype application/pdf
- dc.identifier.citation González-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 1
- dc.identifier.doi http://dx.doi.org/10.1016/j.jid.2016.08.015
- dc.identifier.issn 0022-202X
- dc.identifier.uri http://hdl.handle.net/10230/34916
- dc.language.iso eng
- dc.publisher Elsevierca
- dc.relation.ispartof J Invest Dermatol. 2017 Jan;137(1):197-206
- dc.rights © 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/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
- dc.subject.keyword Carcinogenesis
- dc.subject.keyword Gene expression regulation
- dc.subject.keyword Merkel cell carcinoma
- dc.subject.keyword Skin neoplasms
- dc.subject.keyword Tumor suppressor protein p53
- dc.subject.keyword Tumor virus infections
- dc.title Shared oncogenic pathways implicated in both virus-positive and UV-induced merkel cell carcinomasca
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion