TUMOR SUPPRESSION AND SOMATIC CELL GENETICS

人类肺癌的基因分析表明， 基因可能在癌发生和肿瘤进展过程中失活。以来 肿瘤抑制基因可能有多种功能， 识别和功能分析的综合策略是 必需的.例如，等位基因缺失和体细胞杂种分析是一种有效的方法。 用于确定假定肿瘤的染色体位置 抑制基因我们检查了54例非小细胞支气管炎， 13个多态性重组探针。鳞状细胞 癌（SCC）的杂合性丢失比 腺癌（Ad）或大细胞癌。杂合性缺失 17号染色体在SCC中的阳性率为89%，而在Ad中的阳性率为18%。 p53基因突变是17 p上的一个假定的肿瘤抑制基因， 在人类肺癌中发现。等位基因序列缺失分析 11号染色体揭示了两个通常缺失的区域（11 p13和11p15.5）。 正常人支气管上皮细胞与 HuT 292-DM是一种肺癌细胞系，在体外具有有限的寿命， 在无胸腺裸鼠中无致瘤性。这两项研究都表明 肿瘤抑制基因可能在肺癌发生中起主导作用， 并提供了通过消减分离这些基因的体外模型系统 文库和插入诱变技术。

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.