Department of Pathology, Université de Tours, Centre Hospitalier Universitaire de Tours, Tours Cedex, France; Biologie des infections à polyomavirus team, UMR INRA ISP 1282, Université de Tours, Tours, France; Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany.
Department of Dermatology, Avicenne University Hospital, Bobigny, France.
J Invest Dermatol. 2020 May;140(5):976-985. doi: 10.1016/j.jid.2019.09.026. Epub 2019 Nov 22.
Merkel cell carcinoma (MCC), an aggressive neuroendocrine carcinoma of the skin, is to date the only human cancer known to be frequently caused by a polyomavirus. However, it is a matter of debate which cells are targeted by the Merkel cell polyomavirus (MCPyV) to give rise to the phenotypically multifaceted MCC cells. To assess the lineage of origin of MCPyV-positive MCC, genetic analysis of a very rare tumor combining benign trichoblastoma and MCPyV-positive MCC was conducted by massive parallel sequencing. Although MCPyV was found to be integrated only in the MCC part, six somatic mutations were shared by both tumor components. The mutational overlap between the trichoblastoma and MCPyV-positive MCC parts of the combined tumor implies that MCPyV integration occurred in an epithelial tumor cell before MCC development. Therefore, our report demonstrates that MCPyV-positive MCC can derive from the epithelial lineage.
默克尔细胞癌（Merkel cell carcinoma，MCC）是一种侵袭性神经内分泌皮肤癌，是迄今为止唯一已知的常由多瘤病毒引起的人类癌症。然而，哪种细胞是默克尔细胞多瘤病毒（Merkel cell polyomavirus，MCPyV）的靶细胞，从而产生表型多样的 MCC 细胞，这是一个有争议的问题。为了评估 MCPyV 阳性 MCC 的起源谱系，通过大规模平行测序对一种罕见的良性毛发上皮瘤和 MCPyV 阳性 MCC 相结合的肿瘤进行了遗传分析。尽管仅在 MCC 部分发现 MCPyV 整合，但两个肿瘤成分共享 6 个体细胞突变。联合肿瘤的毛发上皮瘤和 MCPyV 阳性 MCC 部分之间的突变重叠表明，MCPyV 整合发生在 MCC 发展之前的上皮肿瘤细胞中。因此，我们的报告表明，MCPyV 阳性 MCC 可以来源于上皮谱系。
