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Shared Oncogenic Pathways Implicated in Both Virus-Positive and UV-Induced Merkel Cell Carcinomas

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 55e90% 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.

 Fuente: Journal of Investigative Dermatology Volume 137, Issue 1, January 2017, Pages 197-206

Editorial: Elsevier

 Año de publicación: 2017

Nº de páginas: 10

Tipo de publicación: Artículo de Revista

 DOI: 10.1016/j.jid.2016.08.015

ISSN: 0022-202X,1523-1747

Autores/as

CURIEL OLMO, SORAYA

DERDAK, SOPHIA

BELTRAN, SERGI

CASTILLO TRUJILLO, ALFREDO

GUT, MARTHA

SÁNCHEZ PACHECO, ROXANA

ALMARAZ, CARMEN

CERECEDA, LAURA

LLOMBART, BEATRIZ

ANTONIO MANUEL AGRAZ DOBLAS

REVERT ARCE, JOSÉ

LÓPEZ GUERRERO, JOSÉ ANTONIO

MOLLEJO, MANUELA

MARRÓN, PABLO ISIDRO

ORTIZ ROMERO, PABLO

FERNÁNDEZ CUESTA, LYNNETTE

GUT, IVO

CERRONI, LORENZO

MIGUEL ANGEL PIRIS PINILLA