Clin Epigenetics. 2011 Apr;2(1):1-5. doi: 10.1007/s13148-010-0013-3. Epub 2010 Nov 24.
Incorporation of viral DNA may interfere with the normal sequence of human DNA bases on the genetic level or cause secondary epigenetic changes such as gene promoter methylation or histone acetylation. Colorectal cancer (CRC) is the second leading cause of cancer mortality in the USA. Chromosomal instability (CIN) was established as the key mechanism in cancer development. Later, it was found that CRC results not only from the progressive accumulation of genetic alterations but also from epigenetic changes. JC virus (JCV) is a candidate etiologic factor in sporadic CRC. It may act by stabilizing β-catenin, facilitating its entrance to the cell nucleus, initialing proliferation and cancer development. Diploid CRC cell lines transfected with JCV-containing plasmids developed CIN. This result provides direct experimental evidence for the ability of JCV T-Ag to induce CIN in the genome of colonic epithelial cells. The association of CRC hMLH1 methylation and tumor positivity for JCV was recently documented. JC virus T-Ag DNA sequences were found in 77% of CRCs and are associated with promoter methylation of multiple genes. hMLH1 was methylated in 25 out of 80 CRC patients positive for T-Ag (31%) in comparison with only one out of 11 T-Ag negative cases (9%). Thus, JCV can mediate both CIN and aberrant methylation in CRC. Like other viruses, chronic infection with JCV may induce CRC by different mechanisms which should be further investigated. Thus, gene promoter methylation induced by JCV may be an important process in CRC and the polyp-carcinoma sequence.
病毒 DNA 的整合可能会在遗传水平上干扰人类 DNA 碱基的正常序列，或导致次要的表观遗传变化，如基因启动子甲基化或组蛋白乙酰化。结直肠癌（CRC）是美国癌症死亡的第二大主要原因。染色体不稳定性（CIN）被确立为癌症发展的关键机制。后来发现，CRC 的发生不仅源于遗传改变的逐渐积累，还源于表观遗传变化。JC 病毒（JCV）是散发性 CRC 的候选病因。它可能通过稳定β-连环蛋白起作用，促进其进入细胞核，启动增殖和癌症发展。转染含有 JCV 质粒的二倍体 CRC 细胞系发展出 CIN。这一结果为 JCV T-Ag 在结肠上皮细胞基因组中诱导 CIN 的能力提供了直接的实验证据。最近有文献记录了结直肠癌 hMLH1 甲基化与 JCV 肿瘤阳性之间的关联。在 77%的 CRC 中发现了 JCV T-Ag 的 DNA 序列，并且与多个基因的启动子甲基化有关。在 T-Ag 阳性的 80 例 CRC 患者中有 25 例发生 hMLH1 甲基化（31%），而在 T-Ag 阴性的 11 例患者中只有 1 例发生（9%）。因此，JCV 可以在 CRC 中介导 CIN 和异常甲基化。像其他病毒一样，JCV 的慢性感染可能通过不同的机制诱导 CRC，这需要进一步研究。因此，JCV 诱导的基因启动子甲基化可能是 CRC 和息肉-癌序列中的一个重要过程。
