Genomic imbalances in 70 snap-frozen cervical squamous intraepithelial lesions: associations with lesion grade, state of the HPV16 E2 gene and clinical outcome.
Genomic imbalances in 70 snap-frozen cervical squamous intraepithelial lesions: associations with lesion grade, state of the HPV16 E2 gene and clinical outcome.
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DOI：
10.1038/sj.bjc.6602237
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发表时间：
2004-12-13
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
宿主基因组异常可能决定宫颈鳞状上皮内病变（锡尔斯）的自然病程。我们进行了比较基因组杂交分析上皮仔细显微解剖70宫颈锡尔斯，迄今为止最大的系列。与以前的研究相比，我们使用冷冻切片以获得最佳的DNA质量，并检查DNA拷贝数失衡（CNI）模式是否是SIL级别，人乳头瘤病毒（HPV）状态和术后复发的特征。我们在宫颈SIL中发现了更多的CNIs，高级别鳞状上皮内病变（HG-SIL）中的CNIs比低级别鳞状上皮内病变（LG-SIL）中的CNIs更多（P=0.04）。虽然一些CNI在HG-SIL和LG-SIL中的频率相似，但其他CNI，包括1 q，3q和16 q的增益，在HG-SIL中经常发现，但在LG-SIL中没有发现。在HPV 16 E2基因（病毒癌基因转录的阻遏物）缺失的HG-SILs中（P=0.026）和随后复发的HG-SILs中（P=0.04），每例CNI显著更多。我们的数据与宫颈SIL进展中CNIs的连续采集一致。与E2基因缺失相关的CNI频率更高，这支持了高危HPV整合与基因组不稳定性相关的体外证据。需要进一步研究宫颈SIL中特异性宿主基因组异常的临床价值。
Host genomic abnormalities may determine the natural history of cervical squamous intraepithelial lesions (SILs). We undertook comparative genomic hybridisation analysis of epithelium carefully microdissected from 70 cervical SILs, the largest series to date. In contrast to previous studies, we used frozen sections for optimal DNA quality and examined whether patterns of DNA copy number imbalance (CNI) are characteristic of SIL grade, human papillomavirus (HPV) status and postoperative recurrence. We identified more CNIs in cervical SIL than previously described, with more CNIs per case in high-grade squamous intraepithelial lesion (HG-SIL) than in low-grade squamous intraepithelial lesion (LG-SIL) (P=0.04). While some CNIs were seen at similar frequencies in HG-SIL and LG-SIL, others, including gain on 1q, 3q and 16q, were found frequently in HG-SIL but not in LG-SIL. There were significantly more CNIs per case in HG-SILs showing loss of the HPV16 E2 gene (a repressor of viral oncogene transcription) (P=0.026) and in HG-SILs that subsequently recurred (P=0.04). Our data are consistent with sequential acquisition of CNIs in cervical SIL progression. Higher frequency of CNI in association with E2 gene loss supports in vitro evidence that high-risk HPV integration is associated with genomic instability. Further investigation of the clinical value of specific host genomic abnormalities in cervical SIL is warranted.
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10.3
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