Positioning of cervical carcinoma and Burkitt lymphoma translocation breakpoints with respect to the human papillomavirus integration cluster in FRA8C at 8q24.13
Positioning of cervical carcinoma and Burkitt lymphoma translocation breakpoints with respect to the human papillomavirus integration cluster in FRA8C at 8q24.13
复制标题
DOI：
10.1016/j.cancergencyto.2004.01.028
复制
发表时间：
2004-10-01
影响因子：
--
通讯作者：
Brink, AATP
中科院分区：
文献类型：
--
作者：
Ferber, MJ;Eilers, P;Brink, AATP
分子细胞遗传学分析经常显示人乳头瘤病毒（HPV）在宫颈癌细胞易位断点附近整合。我们最近在原发性宫颈癌样本中的 8q24 处共同脆弱位点 FRA8C 的远端描述了一组 HPV 18 整合。染色体带 8q24 包含 MYC 基因（别名 c-MYC）、FRA8C 和 FRA8D。 MYC 基因在各种肿瘤类型中经常失调（通常是通过易位或扩增）。在本研究中，我们使用组合二元比率荧光原位杂交对原发性宫颈癌和 HeLa 细胞中的 HPV18 整合模式和 8q24 易位进行了分子细胞遗传学分析。我们的目的是确定这些事件中涉及的染色体断裂与 MYC 基因的物理关系。它们是否映射到 FRA8C 站点、FRA8D 站点或两者；以及它们如何与 DNA 柔性域的出现相关。 8q24 易位断点映射在 FRA8C 远端的整合 HPV 18 序列片段之间。该区域包含 DNA 螺旋柔性簇，其中几个位于宫颈癌中 HPV 整合位点和易位断点附近。在伯基特淋巴瘤 (BL) 中已知的 MYC 易位断点附近也发现了 DNA 螺旋柔性簇，但大多数 BL 断点明显位于 FRA8C 之外。我们的数据显示，FRA8C 参与宫颈癌中的 HPV 整合和染色体易位；然而，这个脆弱位点不参与大多数 BL 中的经典 MYC 易位。在宫颈癌的家族性背景下，FRA8C可能被认为是宫颈癌的候选易感区。 (C) 2004 Elsevier Inc. 保留所有权利。
Molecular cytogenetic analysis frequently shows human papillomavirus (HPV) integration near translocation breakpoints in cervical cancer cells. We have recently described a cluster of HPV 18 integrations in the distal end of the common fragile site FRA8C at 8q24 in primary cervical carcinoma samples. Chromosome band 8q24 contains the MYC gene (alias c-MYC), FRA8C, and FRA8D. The MYC gene is frequently deregulated-usually by translocation or amplification-in various tumor types. In the present study, we performed a molecular cytogenetic analysis of HPV18 integration patterns and the 8q24 translocation in a primary cervical carcinoma and in HeLa cells using combined binary ratio-fluorescence in situ hybridization. Our aim was to determine how the chromosomal breaks involved in these events relate physically to the MYC gene; whether they map to the FRA8C site, the FRA8D site, or both; and how they correlate with the occurrence of DNA flexibility domains. The 8q24 translocation breakpoints mapped between stretches of integrated HPV 18 sequences in the distal end of FRA8C. This region contained DNA helix flexibility clusters, several of which mapped in the vicinity of HPV integration sites and translocation breakpoints in cervical carcinomas. DNA helix flexibility clusters were also found near known MYC translocation breakpoints in Burkitt lymphomas (BL), but most BL breakpoints mapped clearly outside FRA8C. Our data revealed that FRA8C is involved in HPV integration and chromosomal translocations in cervical carcinoma; however, this fragile site is not involved in classical MYC translocations in most BLs. In the context of the familial nature of cervical cancer, FRA8C may be considered a candidate susceptibility region for cervical carcinoma. (C) 2004 Elsevier Inc. All rights reserved.