Tada M, Omata M, Ohto M
First Department of Internal Medicine, Chiba University School of Medicine, Japan.
Cancer Res. 1990 Feb 15;50(4):1121-4.
The ras gene is one of the oncogenes most commonly detected in human cancers, and it consists of three families (H-ras, K-ras, N-ras). These genes are converted to active oncogenes by point mutations occurring in either codon 12, 13, or 61. We analyzed mutations of these codons in 23 primary hepatic malignant tumors (12 hepatocellular carcinomas, nine cholangiocarcinomas, and two hepatoblastomas) by a method to directly sequence nucleotides, using polymerase chain reaction and a direct sequencing method. Of 23 hepatic malignant tumors, point mutations at K-ras codon 12 or K-ras codon 61 were found in six of nine cholangiocarcinomas. In contrast, there were no point mutations in any of 12 hepatocellular carcinomas or two hepatoblastomas around codon 12, 13, or 61 of the ras genes. These observations suggest that ras gene mutations are not related to pathogenesis of hepatocellular carcinoma, but play an important role in pathogenesis of cholangiocarcinoma.
ras基因是在人类癌症中最常检测到的癌基因之一，它由三个家族（H-ras、K-ras、N-ras）组成。这些基因通过发生在密码子12、13或61的点突变转化为活性癌基因。我们采用聚合酶链反应和直接测序法直接对核苷酸进行测序，分析了23例原发性肝脏恶性肿瘤（12例肝细胞癌、9例胆管癌和2例肝母细胞瘤）中这些密码子的突变情况。在9例胆管癌中，有6例在K-ras密码子12或K-ras密码子61处发现了点突变。相比之下，在12例肝细胞癌或2例肝母细胞瘤中，ras基因密码子12、13或61周围均未发现点突变。这些观察结果表明，ras基因突变与肝细胞癌的发病机制无关，但在胆管癌的发病机制中起重要作用。
