TUMOR SUPPRESSION AND SOMATIC CELL GENETICS

人类肺癌的基因分析表明肿瘤抑制因子 基因可能在癌变和肿瘤进展过程中失活。自.以来 肿瘤抑制基因可能在多种功能类别中，一个 识别和功能分析的综合策略是 必填项。例如，等位基因缺失和体细胞杂交分析是 用于确定假定肿瘤的染色体位置 抑制基因。我们检查了54例非小细胞肺癌 13个多态重组探针与癌的关系。鳞状细胞间 癌(SCC)杂合性缺失的发生率高于 腺癌(Ad)或大细胞癌。基因杂合性丢失 染色体17p在鳞癌中的出现率为89%，而在Ad中为18%。 P53是17p上的一个假定的肿瘤抑制基因，其突变是频繁的。 在人类肺癌中发现。等位基因序列缺失分析 11号染色体显示了两个常见的缺失区域(llpl3和llpl5.5)。 正常人支气管上皮细胞与人支气管上皮细胞的体细胞杂交 HuT292-DM是一种肺癌细胞系，在体外具有有限的寿命和 在裸鼠体内不会致癌。这两项研究都表明 肿瘤抑制基因在肺癌发生中可能起主导作用 并提供了通过差减分离这些基因的体外模型系统 文库和插入突变技术。

Genetic analysis of human lung carcinomas indicate that tumor suppressor genes may be inactivated during carcinogenesis and tumor progression. Since tumor suppressor genes may be in multiple functional classes, a comprehensive strategy for identification and functional analysis is required. For example, allelic deletion and somatic hybrid analyses are being used to identify the chromosomal location of putative tumor suppressor genes. We have examined 54 non-small cell bronchogenic carcinomas with 13 polymorphic recombinant probes. Among squamous cell carcinomas (SCC) loss of heterozygosity was more frequent than among adenocarcinomas (Ad) or large cell carcinomas. Loss of heterozygosity for chromosome 17p was found in 89% of SCC when compared to 18% of Ad. Mutations in p53, a putative tumor suppressor gene on 17p, were frequently found in human lung cancers. Allelic sequence deletion analysis of chromosome 11 revealed two commonly deleted regions (llpl3 and llpl5.5). Somatic cell hybrids between normal human bronchial epithelial cells and HuT292-DM, a lung carcinoma cell line, had a finite life span in vitro and were nontumorigenic in athymic nude mice. Both of these studies suggest that tumor suppressor genes may play a dominant role in lung carcinogenesis and provide in vitro model systems for isolating these genes by subtraction library and insertional mutagenesis technologies.