Loss of heterozygosity and mutational alterations of the p53 gene in skin tumours of interspecific hybrid mice.
Loss of heterozygosity and mutational alterations of the p53 gene in skin tumours of interspecific hybrid mice.
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发表时间：
1991-12
期刊：
影响因子：
8
通讯作者：
Burns Pa;Christopher J. Kemp;Gannon Jv;David P. Lane;R. Bremner;Allan Balmain
中科院分区：
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作者：
Burns Pa;Christopher J. Kemp;Gannon Jv;David P. Lane;R. Bremner;Allan Balmain
肿瘤抑制基因的功能改变或丢失是人类肿瘤进展的重要特征。采用合适的动物模型系统将极大地促进这些基因的检测和操作。在这里，我们描述了一个实验方法，这个问题的基础上，小家鼠和小家鼠之间的F1杂种诱导的皮肤肿瘤的分析。结果表明，13例小鼠皮肤癌中有4例发生11号染色体杂合性丢失，而癌前乳头状瘤中未发生11号染色体杂合性丢失。由于小鼠p53基因位于该染色体上，因此分别对致瘤细胞系和原发性肿瘤DNA进行免疫沉淀和DNA测序研究，以确定p53等位基因的状态。这些研究揭示了p53突变的存在，包括移码和错义，其中一些与人类肿瘤中发现的突变相同。在分化良好的鳞状细胞癌中发现了正常p53功能的丧失，因此似乎并不直接导致进一步进展为未分化的梭形细胞表型。
Functional alterations or loss of tumor-suppressor genes are an important feature of neoplastic progression in humans. The employment of suitable animal model systems would greatly facilitate the detection and manipulation of such genes. We describe here an experimental approach to this problem based on the analysis of skin tumors induced in F1 hybrids between Mus musculus and Mus spretus mice. The results show that loss of heterozygosity on chromosome 11 occurred in 4/13 mouse skin carcinomas, but not in premalignant papillomas. Since the murine p53 gene is located on this chromosome, immunoprecipitation and DNA-sequencing studies were carried out on tumorigenic cell lines and primary tumor DNA respectively to determine the status of p53 alleles. These studies revealed the presence of p53 mutations, both frameshifts and missense, some of which are identical to those found in human tumors. Loss of normal p53 function is found in well-differentiated squamous-cell carcinomas and thus does not appear to be directly responsible for further progression to an undifferentiated spindle cell phenotype.