Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5649844 | Journal of Investigative Dermatology | 2017 | 29 Pages |
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.
Keywords
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Dermatology
Authors
MarÃa del Carmen González-Vela, Soraya Curiel-Olmo, Sophia Derdak, Sergi Beltran, Miguel Santibañez, Nerea MartÃnez, Alfredo Castillo-Trujillo, Martha Gut, Roxana Sánchez-Pacheco, Carmen Almaraz, Laura Cereceda, Beatriz Llombart,