Distinct merkel cell polyomavirus molecular features in tumour and non tumour specimens from patients with merkel cell carcinoma.
Distinct merkel cell polyomavirus molecular features in tumour and non tumour specimens from patients with merkel cell carcinoma.
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DOI：
10.1371/journal.ppat.1001076
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发表时间：
2010-08-26
期刊：
影响因子：
6.7
通讯作者：
Rozenberg F
中科院分区：
文献类型：
--
作者：
Laude HC;Jonchère B;Maubec E;Carlotti A;Marinho E;Couturaud B;Peter M;Sastre-Garau X;Avril MF;Dupin N;Rozenberg F
默克尔细胞多瘤病毒 (MCPyV) 与默克尔细胞癌 (MCC) 相关，默克尔细胞癌是一种罕见的、具有神经内分泌特征的侵袭性皮肤癌。 MCPyV 基因组的单克隆整合和病毒大 T (LT) 抗原在 MCC 细胞中的表达充分表明了 MCPyV 的因果作用。我们通过定量 PCR、测序和整合病毒 DNA 检测，研究并表征了 33 名患者的 MCC、呼吸道、尿液和血液样本中的 MCPyV 分子特征。我们检查了原发性 MCC 中的 MCPyV 病毒载量或 MCPyV DNA 血症与生存之间的关联。根据每个隔室中的病毒分子特征来解释结果。每个细胞含有超过 1 个病毒基因组拷贝的 MCC 患者比每个细胞少于 1 个拷贝的患者获得完全缓解的时间更长（34 个月 vs 10 个月，P = 0.037）。与完全缓解的患者相比，患病患者的外周血单核细胞 (PBMC) 中含有 MCPyV 的频率更高（60% vs 11%，P = 0.00083）。此外，随访期间至少一份 PBMC 样本中检测到 MCPyV 与较短的总生存期相关 (P = 0.003)。对 MCC 和非 MCC 样本中的病毒 DNA 进行测序，确定了常见的单核苷酸多态性，定义了 8 种患者特定毒株。然而，在 8/12 MCC 病例中观察到截断 MCPyV LT 的特定分子特征，但在 15 名患者的呼吸道和尿液样本中未观察到。在 4 个 MCC 病例中发现了新的整合位点。最后，在两名患有播散性 MCC 疾病的患者的 PBMC 中检测到 MCPyV 的突变整合形式，表明存在转移细胞的循环。我们的结论是，原发性 MCC 肿瘤和 PBMC 中的 MCPyV 分子特征可能有助于预测疾病的病程。默克尔细胞多瘤病毒（MCPyV）是最近发现的一种与罕见皮肤癌默克尔细胞癌（MCC）高度相关的病毒。 MCPyV 在癌症中的因果作用通过病毒序列整合到细胞基因组中和特定的分子特征来表明。我们在 33 名 MCC 患者的肿瘤和非肿瘤样本中寻找并比较了 MCPyV 的分子种类。我们发现，每个细胞的肿瘤病毒载量大于 1 个拷贝与更好的结果相关，并且在血液中而非尿液中检测到病毒与较短的总生存期相关。在两名转移性疾病患者的血液中发现了肿瘤特异性分子特征，但在他们的呼吸道样本和尿液样本中并未出现。我们建议将肿瘤和血液中 MCPyV 的分子分析用作 MCC 患者感染和癌症进展的生物标志物。
Merkel Cell Polyomavirus (MCPyV) is associated with Merkel Cell carcinoma (MCC), a rare, aggressive skin cancer with neuroendocrine features. The causal role of MCPyV is highly suggested by monoclonal integration of its genome and expression of the viral large T (LT) antigen in MCC cells. We investigated and characterized MCPyV molecular features in MCC, respiratory, urine and blood samples from 33 patients by quantitative PCR, sequencing and detection of integrated viral DNA. We examined associations between either MCPyV viral load in primary MCC or MCPyV DNAemia and survival. Results were interpreted with respect to the viral molecular signature in each compartment. Patients with MCC containing more than 1 viral genome copy per cell had a longer period in complete remission than patients with less than 1 copy per cell (34 vs 10 months, P = 0.037). Peripheral blood mononuclear cells (PBMC) contained MCPyV more frequently in patients sampled with disease than in patients in complete remission (60% vs 11%, P = 0.00083). Moreover, the detection of MCPyV in at least one PBMC sample during follow-up was associated with a shorter overall survival (P = 0.003). Sequencing of viral DNA from MCC and non MCC samples characterized common single nucleotide polymorphisms defining 8 patient specific strains. However, specific molecular signatures truncating MCPyV LT were observed in 8/12 MCC cases but not in respiratory and urinary samples from 15 patients. New integration sites were identified in 4 MCC cases. Finally, mutated-integrated forms of MCPyV were detected in PBMC of two patients with disseminated MCC disease, indicating circulation of metastatic cells. We conclude that MCPyV molecular features in primary MCC tumour and PBMC may help to predict the course of the disease. Merkel cell polyomavirus (MCPyV) is a recently discovered virus highly associated with a rare skin cancer, Merkel cell carcinoma (MCC). The causal role of MCPyV in cancer is suggested by integration of viral sequences into the cell genome and by a specific molecular signature. We looked for and compared molecular species of MCPyV in tumour and non tumour samples of 33 MCC patients. We showed that a tumour viral load greater than 1 copy per cell was associated with a better outcome, and that detection of the virus in blood but not in urine correlated with a shorter overall survival. A tumour–specific molecular signature was found in the blood of two patients with metastatic disease, but did not occur in their respiratory nor urine samples. We propose that molecular analysis of MCPyV in tumour and blood be used as a biomarker of infection and cancer progression in MCC patients.
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影响因子：
11.8
作者：
Goh, Shan;Lindau, Cecilia;Allander, Tobias
通讯作者：
Allander, Tobias
DOI：
10.1097/pas.0b013e3181aa30a5
发表时间：
2009-09
期刊：
The American journal of surgical pathology
影响因子：
--
作者：
Busam KJ;Jungbluth AA;Rekthman N;Coit D;Pulitzer M;Bini J;Arora R;Hanson NC;Tassello JA;Frosina D;Moore P;Chang Y
通讯作者：
Chang Y
影响因子：
45.3
作者：
Allen, PJ;Bowne, WB;Coit, DG
通讯作者：
Coit, DG
影响因子：
56.9
作者：
Ewald, D;Li, MG;Hennighausen, L
通讯作者：
Hennighausen, L
影响因子：
4.6
作者：
Helmbold, Peter;Lahtz, Christoph;Dammann, Reinhard H.
通讯作者：
Dammann, Reinhard H.