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Merkel Cell Polyomavirus: Oncogenesis in a Stable Genome

Merkel cell polyomavirus (MCV) is the causative agent for the majority of Merkel cell carcinoma (MCC) cases. Polyomavirus-associated MCC (MCCP) is characterized by the integration of MCV DNA into the tumor genome and a low tumor mutational burden. In contrast, nonviral MCC (MCCN) is characterized by...

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Autores principales: Ahmed, Mona M., Cushman, Camille H., DeCaprio, James A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781562/
https://www.ncbi.nlm.nih.gov/pubmed/35062263
http://dx.doi.org/10.3390/v14010058
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author Ahmed, Mona M.
Cushman, Camille H.
DeCaprio, James A.
author_facet Ahmed, Mona M.
Cushman, Camille H.
DeCaprio, James A.
author_sort Ahmed, Mona M.
collection PubMed
description Merkel cell polyomavirus (MCV) is the causative agent for the majority of Merkel cell carcinoma (MCC) cases. Polyomavirus-associated MCC (MCCP) is characterized by the integration of MCV DNA into the tumor genome and a low tumor mutational burden. In contrast, nonviral MCC (MCCN) is characterized by a high tumor mutational burden induced by UV damage. Since the discovery of MCV, much work in the field has focused on understanding the molecular mechanisms of oncogenesis driven by the MCV tumor (T) antigens. Here, we review our current understanding of how the activities of large T (LT) and small T (ST) promote MCC oncogenesis in the absence of genomic instability. We highlight how both LT and ST inhibit tumor suppressors to evade growth suppression, an important cancer hallmark. We discuss ST interactions with cellular proteins, with an emphasis on those that contribute to sustaining proliferative signaling. Finally, we examine active areas of research into open questions in the field, including the origin of MCC and mechanisms of viral integration.
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spelling pubmed-87815622022-01-22 Merkel Cell Polyomavirus: Oncogenesis in a Stable Genome Ahmed, Mona M. Cushman, Camille H. DeCaprio, James A. Viruses Review Merkel cell polyomavirus (MCV) is the causative agent for the majority of Merkel cell carcinoma (MCC) cases. Polyomavirus-associated MCC (MCCP) is characterized by the integration of MCV DNA into the tumor genome and a low tumor mutational burden. In contrast, nonviral MCC (MCCN) is characterized by a high tumor mutational burden induced by UV damage. Since the discovery of MCV, much work in the field has focused on understanding the molecular mechanisms of oncogenesis driven by the MCV tumor (T) antigens. Here, we review our current understanding of how the activities of large T (LT) and small T (ST) promote MCC oncogenesis in the absence of genomic instability. We highlight how both LT and ST inhibit tumor suppressors to evade growth suppression, an important cancer hallmark. We discuss ST interactions with cellular proteins, with an emphasis on those that contribute to sustaining proliferative signaling. Finally, we examine active areas of research into open questions in the field, including the origin of MCC and mechanisms of viral integration. MDPI 2021-12-30 /pmc/articles/PMC8781562/ /pubmed/35062263 http://dx.doi.org/10.3390/v14010058 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Ahmed, Mona M.
Cushman, Camille H.
DeCaprio, James A.
Merkel Cell Polyomavirus: Oncogenesis in a Stable Genome
title Merkel Cell Polyomavirus: Oncogenesis in a Stable Genome
title_full Merkel Cell Polyomavirus: Oncogenesis in a Stable Genome
title_fullStr Merkel Cell Polyomavirus: Oncogenesis in a Stable Genome
title_full_unstemmed Merkel Cell Polyomavirus: Oncogenesis in a Stable Genome
title_short Merkel Cell Polyomavirus: Oncogenesis in a Stable Genome
title_sort merkel cell polyomavirus: oncogenesis in a stable genome
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781562/
https://www.ncbi.nlm.nih.gov/pubmed/35062263
http://dx.doi.org/10.3390/v14010058
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