Detection of Merkel cell polyomavirus with a tumour-specific signature in non-small cell lung cancer.

Detection of Merkel cell polyomavirus with a tumour-specific signature in non-small cell lung cancer.
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DOI:
10.1038/bjc.2012.567
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发表时间:
2013-02-19
影响因子:
8.8
通讯作者:
Daibata, M.
Daibata, M.
中科院分区:
医学1区
文献类型:
--
作者:
Hashida, Y.;Imajoh, M.;Nemoto, Y.;Kamioka, M.;Taniguchi, A.;Taguchi, T.;Kume, M.;Orihashi, K.;Daibata, M.

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我们搜索了非小细胞肺癌(NSCLC)的病毒病因,重点是默克尔细胞多瘤病毒(MCPyV)。我们分析了112例日本非小细胞肺癌的MCPyV基因组的存在和RNA转录和MCPyV编码抗原的表达。我们还对肺癌中MCPyV的分子特征进行了首次分析。PCR结果显示,9/32例鳞状细胞癌(SCC),9/45例腺癌(AC),1/32例大细胞癌和1/3例多形性癌中MCPyV DNA阳性。一些MCPyV DNA阳性癌症表达大T抗原(LT)RNA转录物。免疫组化显示肿瘤细胞中表达MCPyV LT抗原。在一个SCC和一个AC中鉴定出病毒整合位点。一个既有附加型又有整合/截短型。另一个携带整合的MCPyV基因组,LT基因中存在移码突变。我们已经证明了一种病毒癌蛋白的表达,存在整合的MCPyV,和一个截短的LT基因与保留的视网膜母细胞瘤肿瘤抑制蛋白结合结构域在NSCLC。尽管病毒流行率较低,但肿瘤特异性分子特征支持MCPyV与一部分患者的NSCLC发病机制部分相关的可能性。
We searched for a viral aetiology for non-small cell lung cancer (NSCLC), focusing on Merkel cell polyomavirus (MCPyV). We analysed 112 Japanese cases of NSCLC for the presence of the MCPyV genome and the expressions of RNA transcripts and MCPyV-encoded antigen. We also conducted the first analysis of the molecular features of MCPyV in lung cancers. PCR revealed that 9 out of 32 squamous cell carcinomas (SCCs), 9 out of 45 adenocarcinomas (ACs), 1 out of 32 large-cell carcinomas, and 1 out of 3 pleomorphic carcinomas were positive for MCPyV DNA. Some MCPyV DNA-positive cancers expressed large T antigen (LT) RNA transcripts. Immunohistochemistry showed that MCPyV LT antigen was expressed in the tumour cells. The viral integration sites were identified in one SCC and one AC. One had both episomal and integrated/truncated forms. The other carried an integrated MCPyV genome with frameshift mutations in the LT gene. We have demonstrated the expression of a viral oncoprotein, the presence of integrated MCPyV, and a truncated LT gene with a preserved retinoblastoma tumour-suppressor protein-binding domain in NSCLCs. Although the viral prevalence was low, the tumour-specific molecular signatures support the possibility that MCPyV is partly associated with the pathogenesis of NSCLC in a subset of patients.
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