Whole genome tiling path array CGH analysis of segmental copy number alterations in cervical cancer cell lines
Whole genome tiling path array CGH analysis of segmental copy number alterations in cervical cancer cell lines
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DOI：
10.1002/ijc.22335
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发表时间：
2007-01-15
影响因子：
6.4
通讯作者：
Lam, Wan L.
中科院分区：
文献类型：
--
作者：
Lockwood, William W.;Coe, Bradley P.;Lam, Wan L.
宫颈癌是世界范围内女性中第二常见的恶性肿瘤，人乳头瘤病毒（HPV）的高危亚型构成主要病原体。然而，只有一小部分感染该病毒的妇女会发病，这表明额外的宿主遗传改变对疾病进展是必要的。在这项研究中，我们研究了一个面板的常用模型宫颈癌细胞系的基因组使用最近开发的全基因组拼接路径阵列CGH分析。基因组图谱的详细分析使许多新的畸变，这可能是错过了传统的细胞遗传学方法的检测。总共鉴定了27个可能参与肿瘤发生的复发性拷贝数改变的最小区域。有趣的是，与浸润性宫颈癌的前驱病变进展相关的3q增益的精细映射确定了与先前候选者不同的最小区域的改变。新的区域的基因扩增，包括共同扩增的Birc和MMP基因簇的11 q22，也是显而易见的。最后，在HPV整合位点的基因组结构的表征确定了SiHa和SW 756中病毒-宿主基因组边界之间的宿主细胞序列的拷贝数增加，表明HPV整合在引发宫颈癌的遗传异常的发展中的直接作用。这项工作代表了迄今为止对宫颈癌基因组的最高分辨率观察，并提供了这些癌细胞系改变状态的明确表征。(c)2006 Wiley-Liss，Inc.
Cervical cancer is the second most common malignancy in women worldwide, with high risk subtypes of human papillomavirus (HPV) constituting the major etiological agent. However, only a small percentage of women infected by the virus develop disease, suggesting that additional host genetic alterations are necessary for disease progression. In this study we examined the genomes of a panel of commonly used model cervical cancer cell lines using a recently developed whole genome tiling path array for CGH analysis. Detailed analysis of genomic profiles enabled the detection of many novel aberrations, which may have been missed by conventional cytogenetic methods. In total, 27 minimal regions of recurrent copy number alteration were identified that are potentially involved in tumorigenesis. Interestingly, fine mapping of the 3q gain, which is associated with the progression of precursor lesions to invasive cervical cancer, identified a minimal region of alteration harboring genes distinct from previous candidates. Novel regions of gene amplification, including the coamplification of both the Birc and MMP gene clusters on 11q22, were also evident. Lastly, characterization of genomic structure at sites of HPV integration identified the copy number gain of host cellular sequences between the viral-host genomic boundaries in both SiHa and SW756, suggesting a direct role for HPV integration in the development of genetic abnormalities that initiate cervical cancer. This work represents the highest resolution look at a cervical cancer genome to date and offers definitive characterization of the alteration status of these cancer cell lines. (c) 2006 Wiley-Liss, Inc.