Hampton G M, Penny L A, Baergen R N, Larson A, Brewer C, Liao S, Busby-Earle R M, Williams A W, Steel C M, Bird C C
Molecular Genetics Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92318.
Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6953-7. doi: 10.1073/pnas.91.15.6953.
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 cryostat-sectioning 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.
人乳头瘤病毒（HPV）所谓的“侵袭性”亚型感染宫颈上皮细胞似乎是宫颈癌病因中的一个重要因素。然而，越来越多的证据表明，进展为浸润性癌还需要其他基因改变。功能研究表明，人类11号染色体含有一个或多个能够抑制源自不同组织病理学类型宫颈癌的细胞系致瘤性的基因，这表明该基因的畸变可能代表致瘤进展所需的至少一种其他改变。为了确定该基因可能的染色体位置，我们对32例宫颈癌患者的原发性肿瘤中的11号染色体进行了系统的基因分析。使用16个高度多态性标记，其中10个基于通过PCR分型的简单序列重复，来比较来自未受累组织的匹配DNA样本以及通过冷冻切片技术高度富集肿瘤细胞的肿瘤组织部分。在检查的32例患者中，14例（44%）表现出克隆性基因改变，导致一个或多个标记的杂合性缺失。11号染色体上的7种克隆性基因改变特异于长臂，这些改变与其他等位基因缺失之间的重叠表明，与宫颈癌相关的一个抑癌基因定位于11号染色体的q22 - q24区域。
