Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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SHR Neuro Krebs Kardio Lipid

González-Vela, MDC; 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, MÁ; Vaqué, JP.
Shared Oncogenic Pathways Implicated in Both Virus-Positive and UV-Induced Merkel Cell Carcinomas.
J Invest Dermatol. 2017; 137(1):197-206 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Cerroni Lorenzo
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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. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing)
Aged -
Aged, 80 and over -
Biomarkers, Tumor - genetics
Biopsy, Needle -
Carcinogenesis - genetics
Carcinoma, Merkel Cell - genetics
Carcinoma, Merkel Cell - mortality
Carcinoma, Merkel Cell - pathology
Carcinoma, Merkel Cell - virology
Cohort Studies -
Female -
Gene Expression Regulation, Neoplastic -
Humans -
Immunohistochemistry -
Male -
Merkel cell polyomavirus - genetics
Merkel cell polyomavirus - isolation & purification
Multivariate Analysis -
Mutation -
Oncogenes - genetics
Prognosis -
Risk Assessment -
Signal Transduction - genetics
Skin Neoplasms - genetics
Skin Neoplasms - mortality
Skin Neoplasms - pathology
Skin Neoplasms - virology
Survival Analysis -
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
Tumor Virus Infections - mortality
Tumor Virus Infections - pathology
Ultraviolet Rays - adverse effects

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