Mitsudomi T, Viallet J, Mulshine J L, Linnoila R I, Minna J D, Gazdar A F
NCI-Navy Medical Oncology Branch, National Cancer Institute, Bethesda, Maryland 20889-5105.
Oncogene. 1991 Aug;6(8):1353-62.
We screened a panel of 103 human lung cancer cell lines for the presence of point mutations at codons 12, 13 or 61 of the human K-, H- and N-ras genes, using restriction fragment length polymorphisms (RFLP), created through mismatched primers during polymerase chain reaction (PCR) of genomic DNA. We found ras mutations in 22/61 (36%) non-small-cell lung cancer (NSCLC) cell lines, predominantly in K-ras codon 12. Identical mutations were present in uncultured tumor materials corresponding to 11 cell lines containing mutated ras genes. ras mutations were found not only in adenocarcinoma cell lines (9/32, 28%), but also in cell lines derived from other types of NSCLC (13/29, 45%). In contrast, none of 37 small-cell lung cancer (SCLC) cell lines and five extra-pulmonary small-cell cancer cell lines had ras mutations. ras mutations were not correlated with sex of the patients, tumor extent, prior therapy status or in vitro culture time. G to T or A to T transversions were the most common base substitutions, occurring in codons 12 and 61 respectively. We conclude that ras mutations play a role in the pathogenesis of a subset of NSCLC but are not involved in SCLC.
我们使用通过基因组DNA聚合酶链反应（PCR）期间错配引物产生的限制性片段长度多态性（RFLP），对103个人类肺癌细胞系进行筛查，以检测人类K-、H-和N-ras基因密码子12、13或61处的点突变。我们在22/61（36%）的非小细胞肺癌（NSCLC）细胞系中发现了ras突变，主要位于K-ras密码子12处。在对应于11个含有突变ras基因的细胞系的未培养肿瘤材料中存在相同的突变。ras突变不仅在腺癌细胞系中被发现（9/32，28%），也在源自其他类型NSCLC的细胞系中被发现（13/29，45%）。相比之下，37个小细胞肺癌（SCLC）细胞系和5个肺外小细胞癌细胞系均未发现ras突变。ras突变与患者性别、肿瘤范围、既往治疗状态或体外培养时间无关。G到T或A到T的颠换是最常见的碱基替换，分别发生在密码子12和61处。我们得出结论，ras突变在一部分NSCLC的发病机制中起作用，但不参与SCLC的发病。
