{"title":"默克尔细胞癌的分子发病机制。","authors":"James A DeCaprio","doi":"10.1146/annurev-pathmechdis-012419-032817","DOIUrl":null,"url":null,"abstract":"<p><p>Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin with two distinct etiologies. Clonal integration of Merkel cell polyomavirus DNA into the tumor genome with persistent expression of viral T antigens causes at least 60% of all MCC. UV damage leading to highly mutated genomes causes a nonviral form of MCC. Despite these distinct etiologies, both forms of MCC are similar in presentation, prognosis, and response to therapy. At least three oncogenic transcriptional programs feature prominently in both forms of MCC driven by the virus or by mutation. Both forms of MCC have a high proliferative growth rate with increased levels of cell cycle-dependent genes due to inactivation of the tumor suppressors RB and p53, a strong MYC signature due to MYCL activation by the virus or gene amplification, and an attenuated neuroendocrine differentiation program driven by the ATOH1 transcription factor.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"16 ","pages":"69-91"},"PeriodicalIF":28.4000,"publicationDate":"2021-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-pathmechdis-012419-032817","citationCount":"42","resultStr":"{\"title\":\"Molecular Pathogenesis of Merkel Cell Carcinoma.\",\"authors\":\"James A DeCaprio\",\"doi\":\"10.1146/annurev-pathmechdis-012419-032817\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin with two distinct etiologies. Clonal integration of Merkel cell polyomavirus DNA into the tumor genome with persistent expression of viral T antigens causes at least 60% of all MCC. UV damage leading to highly mutated genomes causes a nonviral form of MCC. Despite these distinct etiologies, both forms of MCC are similar in presentation, prognosis, and response to therapy. At least three oncogenic transcriptional programs feature prominently in both forms of MCC driven by the virus or by mutation. Both forms of MCC have a high proliferative growth rate with increased levels of cell cycle-dependent genes due to inactivation of the tumor suppressors RB and p53, a strong MYC signature due to MYCL activation by the virus or gene amplification, and an attenuated neuroendocrine differentiation program driven by the ATOH1 transcription factor.</p>\",\"PeriodicalId\":50753,\"journal\":{\"name\":\"Annual Review of Pathology-Mechanisms of Disease\",\"volume\":\"16 \",\"pages\":\"69-91\"},\"PeriodicalIF\":28.4000,\"publicationDate\":\"2021-01-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1146/annurev-pathmechdis-012419-032817\",\"citationCount\":\"42\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annual Review of Pathology-Mechanisms of Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1146/annurev-pathmechdis-012419-032817\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2020/11/23 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual Review of Pathology-Mechanisms of Disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1146/annurev-pathmechdis-012419-032817","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/11/23 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin with two distinct etiologies. Clonal integration of Merkel cell polyomavirus DNA into the tumor genome with persistent expression of viral T antigens causes at least 60% of all MCC. UV damage leading to highly mutated genomes causes a nonviral form of MCC. Despite these distinct etiologies, both forms of MCC are similar in presentation, prognosis, and response to therapy. At least three oncogenic transcriptional programs feature prominently in both forms of MCC driven by the virus or by mutation. Both forms of MCC have a high proliferative growth rate with increased levels of cell cycle-dependent genes due to inactivation of the tumor suppressors RB and p53, a strong MYC signature due to MYCL activation by the virus or gene amplification, and an attenuated neuroendocrine differentiation program driven by the ATOH1 transcription factor.
期刊介绍：
The Annual Review of Pathology: Mechanisms of Disease is a scholarly journal that has been published since 2006. Its primary focus is to provide a comprehensive overview of recent advancements in our knowledge of the causes and development of significant human diseases. The journal places particular emphasis on exploring the current and evolving concepts of disease pathogenesis, as well as the molecular genetic and morphological changes associated with various diseases. Additionally, the journal addresses the clinical significance of these findings.
In order to increase accessibility and promote the broad dissemination of research, the current volume of the journal has transitioned from a gated subscription model to an open access format. This change has been made possible through the Annual Reviews' Subscribe to Open program, which allows all articles published in this volume to be freely accessible to readers. As part of this transition, all articles in the journal are published under a Creative Commons Attribution (CC BY) license, which encourages open sharing and use of the research.
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