한국인 구강 편평 세포 암종에서의 H-ras, K-ras 유전자의 돌연변이

H-ras, K-ras gene mutation in the oral squamous cell carcinomas of Korean

Oncogenes are altered cellular genes that disrupt the control systems of cell growth and/or cell differentiation and in this way contribute to the development of cancer, Mutations in cellular ras genes have been implicated in this process. The development of oral squamous cell carcinoma has traditionally been linked with exposure to mutagens in tobacco. Members of the ras gene family are thought to be common targets for mutagenesis in a wide range of animal and human cancer. Activation of ras genes frequently involves a single point mutation at specific sites within exon one(codon 12, 13) or exon two(codon 61)and results in the expression of an abnormal p21 protein harbouring a single amino acid substitution at areas important for guanin nucleotide binding, favouring the active GTP-bound state. Point mutations in ras genes have been detected in various human cancers, although the incidence varies with tumor type and site. These findings may reflect the fact that ras point mutations appear to be carcinogen-specific. The purpose of this study was to analyse H-ras, K-ras of oral squamous cell carcinoma which is formalin-fixed, paraffin-embedded samples associated with clinico-pathologic parameters. Twenty cases were screened to find out mutations in exon 1, 2 of H-ras genes by PCR, single strand conformation polymorphism, followed by direct sequencing of PCR-amplified DNA. The results are as follows : 1. Most of the cases were advanced moderate to well differentiated squamous cell carcinoma which have not correlation to clinical findings such as site, smoking history, clinical stage. 2. In single strand conformation polymorphism, there in no abnormal mobility in H-ras, K-ras exon 1 and 2. Changing of gel condition such as temperature, glycerol concentration showed same result. 3. Direct sequencing of PCR product revealed wild-type H-ras and K-ras gene. 4. ras gene mutation could not find in both group of smokers and nonsmokers, thus smoking in Korean people may not affect the ras genes. In conclusion, the results of this study show that ras point mutations in oral squamous cell carcinoma are infrequent, at least in Korean examples of oral cancer, despite the probable importance of chemical carcinogens in the etiology of the disease. Ras mutations may contribute, but are not fundamental, to oral cancer development. Future studies will therefore extend these investigation in conjunction with ras gene amplification, intronic mutation, and other oncogenes and tumor suppressor genes.