GRCh38 · COSMIC v95

Summary

This section shows a summary for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.

Reference
Shared oncogenic pathways implicated in both virus-positive and UV-induced Merkel Cell Carcinomas.
Paper ID
COSP42254
Authors
González-Vela MC, Curiel-Olmo S, Derdak S, Beltran S, Santibañez M, Martínez N, Castillo-Trujillo A, Gut M, Sánchez-Pacheco R, Almaraz C, Cereceda L, Llombart B, Agraz-Doblas A, Revert-Arce J, López Guerrero JA, Mollejo M, Marrón PI, Ortiz-Romero P, Fernandez-Cuesta L, Varela I, Gut I, Cerroni L, Piris MA and Vaqué JP
Affiliation
Pathology Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain; Cancer Genomics Laboratory, Instituto de Investigación Marqués de Valdecilla, IDIVAL, Santander, Spain.
Journal
The Journal of investigative dermatology, 2016
ISSN: 1523-1747
PMID: 27592799 (view at PubMed or Europe PMC)
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 (MCPyV) can play in 55% to 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, MCPyV-negative tumors had higher mutational loads with UV signatures and more frequent mutations in TP53 and RB compared with their MCPyV-positive counterparts. Surprisingly, despite important genetic differences, the two MCC etiologies both exhibited nuclear accumulation of oncogenic transcription factors such as NFAT, P-CREB and P-STAT3, indicating commonly deregulated pathogenic mechanisms with the potential to serve as targets for therapy. A multivariable analysis identified P-CREB as an independent survival factor with respect to clinical variables and MCPyV status in our cohort of MCC patients.
Paper Status
Curated