Genetic events associated with human endometrial carcinogenesis.

本研究旨在揭示多种遗传事件在人子宫内膜肿瘤转化中的作用。微细胞介导的1号染色体向子宫内膜癌细胞的转移与肿瘤发生性和体外生长特性的抑制有关，表明1号染色体上存在肿瘤抑制基因。子宫内膜癌细胞与正常成纤维细胞之间的非致瘤性全细胞杂交中4号染色体的缺失与致瘤性的恢复相关。除此之外，对ras基因的等位基因丢失和点突变的综合分析表明，至少有3个遗传事件，包括K-ras基因的18q、17p缺失和密码子12点突变，与子宫内膜癌的发生有关。这些等位基因丢失的可能目标分别是DCC基因和p53基因序列。位于1号染色体上的推定抑制基因参与了细胞异型性增生病灶的形成，这可以通过含有1号染色体额外拷贝的微细胞杂交中转化表型的改变来推测。涉及K-ras基因突变、DCC基因缺失和4号染色体缺失的遗传事件对应于从增生到瘤变的转变。p53基因突变似乎与完全恶性肿瘤发展后的进展有关。

The present study was undertaken to disclose the involvement of multiple genetic events in neoplastic transformation of human endometrium. Microcell mediated a chromosome 1 transfer into endometrial carcinoma cells associated with the suppression of tumorigenecity and in vitro growth properties, suggesting the presence of tumor suppressor gene(s) on chromosome 1. Loss of chromosome 4 from the nontumorigenic whole cell hybrids between endometrial carcinoma cells and normal fibroblasts correlated with the recovery of tumorigenecity. In addition to these results, comprehensive analyses of allelic losses and point mutations of ras genes disclosed that at least 3 genetic events, including 18q, 17p deletions, and point mutations at codon 12 of the K-ras gene, were implicated in the development of endometrial carcinomas. Likely targets for these allelic losses were the DCC gene and the p53 gene sequences, respectively. The involvement of putative suppressor gene(s) locating on chromosome 1 in formation of hyperplastic focus with cellular atypism may be speculated by alterations of transformed phenotypes in the microcell hybrid containing an extra copy of chromosome 1. The genetic events implicating K-ras gene mutatin, loss of DCC gene and chromosome 4 deletion corresponded to the transition from hyperplasia to neoplasia. The p53 gene mutations seemed to be implicated in the progression following the development of fully malignant tumors.