Department of Hematopathology, MD Anderson Cancer Center, Houston, Texas, USA.
J Virol. 2013 Aug;87(16):8916-26. doi: 10.1128/JVI.00340-13. Epub 2013 Jun 5.
Elucidation of tumor-DNA virus associations in many cancer types has enhanced our knowledge of fundamental oncogenesis mechanisms and provided a basis for cancer prevention initiatives. RNA-Seq is a novel tool to comprehensively assess such associations. We interrogated RNA-Seq data from 3,775 malignant neoplasms in The Cancer Genome Atlas database for the presence of viral sequences. Viral integration sites were also detected in expressed transcripts using a novel approach. The detection capacity of RNA-Seq was compared to available clinical laboratory data. Human papillomavirus (HPV) transcripts were detected using RNA-Seq analysis in head-and-neck squamous cell carcinoma, uterine endometrioid carcinoma, and squamous cell carcinoma of the lung. Detection of HPV by RNA-Seq correlated with detection by in situ hybridization and immunohistochemistry in squamous cell carcinoma tumors of the head and neck. Hepatitis B virus and Epstein-Barr virus (EBV) were detected using RNA-Seq in hepatocellular carcinoma and gastric carcinoma tumors, respectively. Integration sites of viral genes and oncogenes were detected in cancers harboring HPV or hepatitis B virus but not in EBV-positive gastric carcinoma. Integration sites of expressed viral transcripts frequently involved known coding areas of the host genome. No DNA virus transcripts were detected in acute myeloid leukemia, cutaneous melanoma, low- and high-grade gliomas of the brain, and adenocarcinomas of the breast, colon and rectum, lung, prostate, ovary, kidney, and thyroid. In conclusion, this study provides a large-scale overview of the landscape of DNA viruses in human malignant cancers. While further validation is necessary for specific cancer types, our findings highlight the utility of RNA-Seq in detecting tumor-associated DNA viruses and identifying viral integration sites that may unravel novel mechanisms of cancer pathogenesis.
阐明许多癌症类型中的肿瘤与 DNA 病毒的关联，增强了我们对基本致癌机制的认识，并为癌症预防措施提供了基础。RNA-Seq 是一种全面评估这种关联的新工具。我们利用 RNA-Seq 分析了癌症基因组图谱数据库中 3775 种恶性肿瘤的 RNA-Seq 数据，以确定病毒序列的存在。我们还利用一种新方法在表达的转录本中检测病毒整合位点。比较了 RNA-Seq 的检测能力与现有的临床实验室数据。在头颈部鳞状细胞癌、子宫内膜样腺癌和肺癌中，通过 RNA-Seq 分析检测到了人乳头瘤病毒 (HPV) 的转录本。在头颈部鳞状细胞癌肿瘤中，HPV 的 RNA-Seq 检测与原位杂交和免疫组化检测结果相关。在肝癌和胃癌中，通过 RNA-Seq 检测到了乙型肝炎病毒和 Epstein-Barr 病毒 (EBV)。在携带 HPV 或乙型肝炎病毒的癌症中检测到了病毒基因和癌基因的整合位点，但在 EBV 阳性的胃癌中没有检测到。表达的病毒转录本的整合位点经常涉及宿主基因组的已知编码区。在急性髓性白血病、皮肤黑色素瘤、脑的低级别和高级别胶质瘤以及乳腺、结肠和直肠、肺、前列腺、卵巢、肾脏和甲状腺的腺癌中，均未检测到 DNA 病毒转录本。总之，本研究提供了人类恶性肿瘤中 DNA 病毒的大规模概述。虽然特定癌症类型需要进一步验证，但我们的研究结果强调了 RNA-Seq 在检测肿瘤相关 DNA 病毒和鉴定可能揭示癌症发病机制新机制的病毒整合位点方面的实用性。
