Yokota J, Wada M, Shimosato Y, Terada M, Sugimura T
National Cancer Center Research Institute, Tokyo, Japan.
Proc Natl Acad Sci U S A. 1987 Dec;84(24):9252-6. doi: 10.1073/pnas.84.24.9252.
By a molecular genetic approach using polymorphic DNA markers that detect allelic deletion of specific chromosomal regions, we analyzed for possible loss of chromosomal heterozygosity in five different histological types of lung cancers obtained from 47 patients. In small-cell carcinomas, the incidence of allelic deletions at three different chromosomal loci was extremely high; loss of heterozygosity was detected on chromosomes 3p in 7 of 7 patients (100%), 13q in 10 of 11 patients (91%), and 17p in 5 of 5 patients (100%). The deletions at these loci in small-cell carcinomas were observed even in the tumors without any clinical evidence of metastasis. Furthermore, loss of heterozygosity on chromosomes 3p and 13q occurred prior to NMYC amplification and chromosome 11p deletion. Loss of heterozygosity on chromosome 3p was also detected with high frequency in adenocarcinomas [5 of 6 patients (83%)]. Heterozygosity of chromosomes 13q and 17p was lost in 10 of 31 patients (32%) and in 3 of 12 patients (25%), respectively, of lung cancers other than small-cell carcinomas. These results indicate that recessive genetic changes involving sequences on chromosomes 3p, 13q, and 17p may play important roles in the genesis of small-cell carcinoma, and those on chromosome 3p may play an important role in the genesis of adenocarcinoma.
通过使用可检测特定染色体区域等位基因缺失的多态性DNA标记的分子遗传学方法，我们分析了从47例患者获得的五种不同组织学类型肺癌中染色体杂合性可能的缺失情况。在小细胞癌中，三个不同染色体位点的等位基因缺失发生率极高；在7例患者中的7例（100%）检测到3号染色体短臂（3p）杂合性缺失，11例患者中的10例（91%）检测到13号染色体长臂（13q）杂合性缺失，5例患者中的5例（100%）检测到17号染色体短臂（17p）杂合性缺失。即使在没有任何转移临床证据的肿瘤中也观察到小细胞癌这些位点的缺失。此外，3p和13q染色体上的杂合性缺失发生在NMYC扩增和11号染色体短臂缺失之前。在腺癌中也高频检测到3p染色体杂合性缺失[6例患者中的5例（83%）]。在非小细胞癌的肺癌中，13q和17p染色体杂合性缺失分别在31例患者中的10例（32%）和12例患者中的3例（25%）中出现。这些结果表明，涉及3p、13q和17p染色体序列的隐性遗传变化可能在小细胞癌的发生中起重要作用，而3p染色体上的变化可能在腺癌的发生中起重要作用。
