Merkel 细胞多瘤病毒在 Merkel 细胞癌中的遗传变异性和整合。
Genetic variability and integration of Merkel cell polyomavirus in Merkel cell carcinoma.
机构信息
Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Paris, France.
出版信息
Virology. 2012 May 10;426(2):134-42. doi: 10.1016/j.virol.2012.01.018. Epub 2012 Feb 16.
Merkel cell polyomavirus (MCPyV) is associated to Merkel cell carcinoma (MCC). We studied 113 MCC tumoral skin lesions originating from 97 patients. MCPyV detection was higher in fresh-frozen (FF) biopsies (94%) than in formalin-fixed paraffin-embedded biopsies (39-47%). Mean viral load in FF tumor was of 7.5 copies per cell with a very wide range (0.01-95.4). Nineteen complete sequences of LTAg were obtained, mainly from FF biopsies when the viral load was high. Seventeen showed stop codons, all localized downstream of the pRb protein binding domain. Sequence comparison and phylogenetic analysis showed that all sequences clustered in the large C clade of MCPyV strains. MCPyV integration was demonstrated in 19 out of 27 FF MCC DNA biopsies without evidence of specific host cellular genome integration site. In 13/19 cases, the viral junction was located within the second exon of the LTAg, after the pRB binding domain.
默克尔细胞多瘤病毒（MCPyV）与默克尔细胞癌（MCC）有关。我们研究了 97 名患者的 113 例 MCC 皮肤肿瘤病变。新鲜冷冻（FF）活检中 MCPyV 的检出率（94%）高于福尔马林固定石蜡包埋（FFPE）活检（39-47%）。FF 肿瘤中的平均病毒载量为每细胞 7.5 个拷贝，范围很宽（0.01-95.4）。获得了 19 个 LTAg 的完整序列，主要来自 FF 活检，当时病毒载量很高。17 个显示终止密码子，全部位于 pRb 蛋白结合域的下游。序列比较和系统发育分析表明，所有序列均聚集在 MCPyV 株的大 C 枝上。在 27 例无 FF MCC DNA 活检中，有 19 例证明存在 MCPyV 整合，没有特定宿主细胞基因组整合位点的证据。在 13/19 例中，病毒连接处位于 LTAg 的第二个外显子内，位于 pRB 结合域之后。
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