Keohavong P, DeMichele M A, Melacrinos A C, Landreneau R J, Weyant R J, Siegfried J M
Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15238, USA.
Clin Cancer Res. 1996 Feb;2(2):411-8.
The K-ras mutation is one of the most common genetic alterations found in human lung cancer. To evaluate the prognostic value of ras gene alterations in lung cancer in a U.S. population, we have screened 173 human lung tumors, which included 127 adenocarcinomas, 37 squamous carcinomas, and 9 adenosquamous carcinomas, for mutations in the K-ras gene using the combination of the PCR and denaturing gradient gel electrophoresis. Forty-three tumors contained K-ras mutations. Of these, 41 were identified among the adenocarcinomas (32%), 1 among the squamous carcinomas (2.7%), and 1 among the adenosquamous carcinomas (11%). Forty of these mutations were found in codon 12 and consisted of 24 G to T transversions, 12 G to A transitions, 2 G to C transversions, and 1 double GG to TT mutation. Two other G to T transversions were found in codon 13, and 1 A to C transversion was found in codon 61. The data showed that gender did not seem to affect the incidence and the types of the K-ras mutations or amino acid changes. Examination of the mutations in adenocarcinomas in relation to overall survival showed no difference in adenocarcinomas with K-ras mutations compared with K-ras-negative adenocarcinomas. However, the substitution of the wild-type GGT (glycine) at codon 12 with a GTT (valine) or a CGT (arginine) showed a strong trend (P = 0.07) toward a poorer prognosis compared with wild-type or other amino acid substitutions. Substitution of the wild-type glycine for aspartate (GAT) showed a strong trend (P = 0.06) for a better outcome than the valine or arginine substitution. Although these trends will require larger patient populations for verification, these data suggest that the prognostic significance of K-ras mutations may depend on the amino acid substitution in the p21(ras) protein.
K-ras突变是人类肺癌中最常见的基因改变之一。为了评估ras基因改变在美国人群肺癌中的预后价值，我们使用聚合酶链反应（PCR）和变性梯度凝胶电泳相结合的方法，对173例人类肺肿瘤进行了K-ras基因突变筛查，其中包括127例腺癌、37例鳞癌和9例腺鳞癌。43个肿瘤含有K-ras突变。其中，41个在腺癌中被鉴定出来（32%），1个在鳞癌中（2.7%），1个在腺鳞癌中（11%）。这些突变中有40个位于密码子12，包括24个G到T的颠换、12个G到A的转换、2个G到C的颠换以及1个GG到TT的双突变。另外2个G到T的颠换位于密码子13，1个A到C的颠换位于密码子61。数据显示，性别似乎不影响K-ras突变的发生率、类型或氨基酸变化。对腺癌中突变与总生存率关系的研究表明，K-ras突变的腺癌与K-ras阴性的腺癌相比无差异。然而，密码子12处野生型GGT（甘氨酸）被GTT（缬氨酸）或CGT（精氨酸）取代，与野生型或其他氨基酸取代相比，显示出预后较差的强烈趋势（P = 0.07）。野生型甘氨酸被天冬氨酸（GAT）取代，与缬氨酸或精氨酸取代相比，显示出预后较好的强烈趋势（P = 0.06）。尽管这些趋势需要更大的患者群体来验证，但这些数据表明K-ras突变的预后意义可能取决于p21(ras)蛋白中的氨基酸取代。
