Genetic analysis for the malignant potential of oral precancerous lesions

1999 Fiscal Year Final Research Report Summary

• Project/Area Number: 10671893
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: KAGOSHIMA UNIVERSITY
• Principal Investigator: YAMAGUCHI Kojiro KAGOSHIMA UNIVERSITY, FACULTY OF DENTISTRY, RESEARCH ASSOCIATE, 歯学部, 助手 (00210360)
• Co-Investigator(Kenkyū-buntansha): KUNIYOSHI Hideharu KAGOSHIMA UNIVERSITY DENTAL HOSPITAL, RESEARCH ASSOCIATE, 歯学部, 助手 (50244249) ; MUKAI Hiroshi KAGOSHIMA UNIVERSITY, FACULTY OF DENTISTRY, ASSOCIATE PROFESSOR, 歯学部, 助教授 (20117550)
• Project Period (FY): 1998 – 1999
• Keywords: genetic alteration / K ras codon 12 / p53 point mutation / 3p LOH / 17p LOH / 17P LOH / K ras codon 12 / 口腔癌

Research Abstract

We have attempted to analyze the genetic alterations and compare the events between oral precancerous lesion (OPL) and oral cancer (OCA) to elucidate the mechanism of cancerization on OPL by using the methods of molecular genetics. Twenty one patients were composed of 7 patients with OCA, 11 with OPL and 3 with both OCA and OPL Both OCA and OPL in an identical patient were included in this study as different cases because they existed separately. Nine of 10 OCAs were diagnosed as squamous cell carcinoma (SCC) and remaining one as verrucous carcinoma. 14OPLs clinically diagnosed as leukoplakia were classified pathologically as 1 slight, 5 mild. Genomic analysis : Point mutation of K-ras codon 12 was analyzed by mutant allele specific amplification method. Replication error (RER) and loss of heterozygosity (LOH) of 2p, 3p, 17p and 18q were analyzed by polymerase chain reaction method. Point mutation of p53 exon 5-8 was analyzed by fluorescence-based polymerase chain reaction single stran d conformation polymorphism method.
Results Genetic alteration was observed in 90% of OCAs and 50% of OPLs. 50% OCAs and 28.6% of OPLs positive for genetic alteration had more than one event. Point mutation of K-ras codon12 was detected in 20% of OCAs and in 14.3% of OPL. Point mutation of p53 exon 5 was detected in 20% of OCAs and in 14.2% of OPL. No point mutation of exon 6 was observed. Point mutation of exon 7 was observed only in one OCA. Point mutation of exon 8 was detected in 20% of OCA and in 21.5% of OPL. On the other hand, LOH at 3p was detected in 30% of OCAs and in 7.1% of OPL. LOH at 17p was detected in 40% of OCAs and in 21.4% of OLP. LOH at 2p was detected in 10% of OCA and in 7.1% of OLP. LOH at 18q was detected only in 20% of OCAs.
Conclusion Accordingly, We think that LOH at 3p and 17p become a guideline that evaluates the malignant potential of precancerous lesion and the mutation of K- ras is thought to have an important role in oral cancerization.. The point mutation of p53 occurred in 28.6% of OPL and increased the incidence in OCA, accounting for 50%. These results suggest that the point mutation of p53 involves strongly in the process and the early event of cancerization.