Shiseki M, Kohno T, Adachi J, Okazaki T, Otsuka T, Mizoguchi H, Noguchi M, Hirohashi S, Yokota J
Biology Division, National Cancer Center Research Institute, Tokyo, Japan.
Genes Chromosomes Cancer. 1996 Oct;17(2):71-7. doi: 10.1002/(SICI)1098-2264(199610)17:2<71::AID-GCC1>3.0.CO;2-Y.
To identify chromosomal loci of tumor suppressor genes involved in the genesis and progression of non-small cell lung carcinoma (NSCLC), comparative allelotype analysis was performed in 23 stage I primary lung tumors and in 22 metastatic lung tumors to the brain. In total, 84 loci on all 22 autosomal chromosomes were examined for loss of heterozygosity (LOH) by restriction fragment length polymorphism (RFLP) analysis with 40 polymorphic DNA probes and polymerase chain reaction (PCR)-LOH analysis of 44 polymorphic loci. LOH on chromosome arms 3p, 13q, and 17p was detected frequently (> 60%) in both stage I primary lung tumors and brain metastases, whereas the incidence of LOH on chromosome arms 2q, 5q, 9p, 12q, 18q, and 22q was more than 60% only in brain metastases. In particular, the incidence of LOH on chromosome arms 2q, 9p, 18q, and 22q in brain metastases was significantly higher than that in stage I primary lung tumors (P < 0.05). These results indicate that tumor suppressor genes on chromosome arms 3p, 13q, and 17p are involved in the genesis of NSCLC, whereas those on several chromosome arms, especially on 2q, 9p, 18q and 22q, play an important role in the progression of NSCLC.
为了确定参与非小细胞肺癌(NSCLC)发生和进展的肿瘤抑制基因的染色体位点,我们对23例I期原发性肺肿瘤和22例脑转移肺肿瘤进行了比较等位基因分型分析。总共通过使用40个多态性DNA探针的限制性片段长度多态性(RFLP)分析以及对44个多态性位点的聚合酶链反应(PCR)-杂合性缺失(LOH)分析,检测了所有22条常染色体上的84个位点的杂合性缺失(LOH)。在I期原发性肺肿瘤和脑转移瘤中均频繁检测到3p、13q和17p染色体臂上的LOH(>60%),而2q、5q、9p、12q、18q和22q染色体臂上的LOH发生率仅在脑转移瘤中超过60%。特别是,脑转移瘤中2q、9p、18q和22q染色体臂上的LOH发生率显著高于I期原发性肺肿瘤(P<0.05)。这些结果表明,3p、13q和17p染色体臂上的肿瘤抑制基因参与了NSCLC的发生,而几个染色体臂上的肿瘤抑制基因,特别是2q、9p、18q和22q染色体臂上的肿瘤抑制基因,在NSCLC的进展中起重要作用。