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Analysis of ras gene mutations in human hepatic malignant tumors by polymerase chain reaction and direct sequencing
1First Department of Internal Medicine, Chiba University School of Medicine, Japan.
Abstract:
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.
Insights
Ras gene mutations are common in cancer. This study found K-ras mutations in cholangiocarcinoma but not in hepatocellular carcinoma, suggesting their role in cholangiocarcinoma development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The ras gene is a frequently observed oncogene in human cancers.
- Ras genes (H-ras, K-ras, N-ras) become active oncogenes through point mutations at specific codons (12, 13, or 61).
Purpose of the Study:
- To investigate the presence and significance of ras gene mutations in primary hepatic malignant tumors.
- To determine if ras gene mutations are associated with hepatocellular carcinoma or cholangiocarcinoma.
Main Methods:
- Analysis of ras gene mutations at codons 12, 13, and 61.
- Utilized polymerase chain reaction and direct nucleotide sequencing.
- Examined 23 primary hepatic malignant tumors: 12 hepatocellular carcinomas, 9 cholangiocarcinomas, and 2 hepatoblastomas.
Main Results:
- Point mutations in K-ras codon 12 or 61 were identified in 6 out of 9 cholangiocarcinomas.
- No ras gene mutations were detected in codons 12, 13, or 61 of the 12 hepatocellular carcinomas or 2 hepatoblastomas.
Conclusions:
- Ras gene mutations do not appear to be involved in the pathogenesis of hepatocellular carcinoma.
- Ras gene mutations play a significant role in the development of cholangiocarcinoma.