del Carmen Gonzalez-Vela, Maria, Curiel-Olmo, Soraya, Derdak, Sophia, Beltran, Sergi ORCID: 0000-0002-2810-3445, Santibanez, Miguel ORCID: 0000-0003-2634-615X, Martinez, Nerea, Castillo-Trujillo, Alfredo, Gut, Martha, Sanchez-Pacheco, Roxana, Almaraz, Carmen, Cereceda, Laura, Llombart, Beatriz, Agraz-Doblas, Antonio, Revert-Arce, Jose, Lopez Guerrero, Jose Antonio, Mollejo, Manuela ORCID: 0000-0001-5658-0532, Isidro Marron, Pablo, Ortiz-Romero, Pablo, Fernandez-Cuesta, Lynnette ORCID: 0000-0002-0724-6703, Varela, Ignacio ORCID: 0000-0002-0969-506X, Gut, Ivo, Cerroni, Lorenzo, Angel Piris, Miguel and Pedro Vaque, Jose (2017). Shared Oncogenic Pathways Implicated in Both Virus-Positive and UV-Induced Merkel Cell Carcinomas. J. Invest. Dermatol., 137 (1). S. 197 - 207. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1747

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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 multi-variable 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
del Carmen Gonzalez-Vela, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Curiel-Olmo, SorayaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Derdak, SophiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beltran, SergiUNSPECIFIEDorcid.org/0000-0002-2810-3445UNSPECIFIED
Santibanez, MiguelUNSPECIFIEDorcid.org/0000-0003-2634-615XUNSPECIFIED
Martinez, NereaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Castillo-Trujillo, AlfredoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gut, MarthaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sanchez-Pacheco, RoxanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Almaraz, CarmenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cereceda, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Llombart, BeatrizUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Agraz-Doblas, AntonioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Revert-Arce, JoseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lopez Guerrero, Jose AntonioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mollejo, ManuelaUNSPECIFIEDorcid.org/0000-0001-5658-0532UNSPECIFIED
Isidro Marron, PabloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ortiz-Romero, PabloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fernandez-Cuesta, LynnetteUNSPECIFIEDorcid.org/0000-0002-0724-6703UNSPECIFIED
Varela, IgnacioUNSPECIFIEDorcid.org/0000-0002-0969-506XUNSPECIFIED
Gut, IvoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cerroni, LorenzoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Angel Piris, MiguelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pedro Vaque, JoseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-243613
DOI: 10.1016/j.jid.2016.08.015
Journal or Publication Title: J. Invest. Dermatol.
Volume: 137
Number: 1
Page Range: S. 197 - 207
Date: 2017
Publisher: ELSEVIER SCIENCE INC
Place of Publication: NEW YORK
ISSN: 1523-1747
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
POLYOMAVIRUS INFECTION; MUTATIONS; CANCER; DIFFERENTIATION; EXPRESSION; MARKERS; GENES; MIBP1; P53Multiple languages
DermatologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/24361

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