LOSS OF HETEROZYGOSITY IN CERVICAL-CARCINOMA - SUBCHROMOSOMAL LOCALIZATION OF A PUTATIVE TUMOR-SUPPRESSOR GENE TO CHROMOSOME 11Q22-Q24
LOSS OF HETEROZYGOSITY IN CERVICAL-CARCINOMA - SUBCHROMOSOMAL LOCALIZATION OF A PUTATIVE TUMOR-SUPPRESSOR GENE TO CHROMOSOME 11Q22-Q24
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DOI：
10.1073/pnas.91.15.6953
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发表时间：
1994-07-19
影响因子：
11.1
通讯作者：
EVANS, GA
中科院分区：
文献类型：
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作者：
HAMPTON, GM;PENNY, LA;EVANS, GA
宫颈上皮细胞被所谓的“侵袭性”人乳头状瘤病毒（HPV）亚型感染似乎是宫颈癌病因学的一个重要因素。然而，越来越多的证据表明，进展为浸润性癌需要额外的基因改变。功能研究表明，人类 11 号染色体含有一个或多个能够抑制来自不同组织病理学类型宫颈癌的细胞系的致瘤性的基因，表明该基因的畸变可能代表致瘤进展所需的至少一种额外变化。为了确定该基因可能的染色体位置，我们对 32 名宫颈癌患者的原发肿瘤中的 11 号染色体进行了系统的遗传分析。使用 16 个高度多态性标记（其中 10 个基于 PCR 分型的简单序列重复）来比较来自非相关组织和通过低温切片技术高度富集肿瘤细胞的肿瘤组织部分的匹配 DNA 样本。在接受检查的 32 名患者中，14 名 (44%) 表现出克隆遗传改变，导致一种或多种标志物杂合性丧失。 11 号染色体上的 7 个克隆遗传改变是长臂特有的，这些和其他等位基因缺失之间的重叠表明与宫颈癌相关的抑制基因映射到染色体 11q22-q24。
Infection of cervical epithelial cells with so-called ''aggressive'' subtypes of human papilloma virus (HPV) appears to be an important factor in the etiology of cervical carcinoma. However, mounting evidence suggests that additional genetic changes are required for progression to an invasive carcinoma. Functional studies have shown that human chromosome 11 contains a gene or genes capable of suppressing tumorigenicity in cell lines derived from different histopathological types of cervical carcinoma, suggesting that aberration of this gene(s) may represent at least one of the additional changes required for tumorigenic progression. To identify the likely chromosomal position of this gene(s), we have carried out a systematic genetic analysis of chromosome 11 in the primary tumors of 32 patients with cervical carcinoma. Sixteen highly polymorphic markers, 10 of which were based on simple sequence repeats typed by PCR, were used to compare matched DNA samples from noninvolved tissue and portions of tumor tissue highly enriched for neoplastic cells by the cryostatsectioning technique. Of the 32 patients examined, 14 (44%) demonstrated clonal genetic alterations resulting in loss of heterozygosity for one or more markers. Seven of the clonal genetic alterations on chromosome 11 were specific to the long arm, and the overlap between these and other allelic deletions suggests that a suppressor gene(s) relevant to cervical carcinoma maps to chromosome 11q22-q24.