A Study Of Ras Gene Mutations And Farnesyltransferase Bata MRNA Expression In Epstein-Barr Virus-Associated Gastric Carcinoma

Objective To analyse the potential pathogenic role of EBV infection,ras mutations and FTase expression in the development of EBV-associated gastric carcinoma (EBVaGC).Methods Ras gene mutations were tested by PCR-RFLP assay and FTase β mRNA expression was tested by RT-PCR assay in 13 EBVaGCs, 45 EBV-negative gastric carcinomas (EBVnGC) with matched clinicopathological parameters and 58 corresponding adjacent tissues of gastric carcinoma.The expression of EBV genes (nuclear antigen EBNA1 and EBNA2 genes,latent membrane protein LMPl and LMP2A gene, and early genes BARF1 and BHRF1 ) was tested by RT-PCR-Southern assay.Results ①H-ras 12 codon mutation was detected in 2 cases of 58 gastric carcinomas (4.44%), all of 2 cases were in EBVnGCs.②The level of FTase β mRNA expression was 0.80 ± 0.19 in 13 EBVaGCs and 0.96±0.43 in 45 EBVnGCs respectively.The difference between the two groups was not significant (t=1.93, P=0.06).The level of FTase β mRNA expression was 0.93±0.39 in 58 gastric carcinomas and 0.78±0.26 in 58 corresponding adjacent tissues respectively.The difference between the two groups was significant (t=2AA, P=0.02<0.05).③ EBNA1 mRNA was detected in all of 13 EBVaGCs,LMP2A mRNA was detected in 5 of 13 cases.while both EBNA2 and LMPl mRNA were negative.Of the 13 EBV-positive samples,6 exhibited BARFl transcripts and 2 exhibited BHRFl transcripts.④The level of FTase P mRNA expression was 0.76 ± 0.24 in 5 LMP2A (0.73 ± 0.19 in 6 BARFl) positive samples and 0.86 ± 0.21 in 8 LMP2A (0.90±0.21 in 7 BARF1) negetive samples of 13 EBVaGCs respectively.The difference between the two groups was not significant (p>0.05).Conclusion ①The rate of ras gene mutations in gastric carcinomas is low.Ras gene mutations was not related with the development of EBVaGC.②There is no relation between the expression of FTase β mRNA and ras gene mutation. Farnesylated proteins other than Ras are likely have a direct role in tumorigenesis.③The lower level of FTase β mRNA expression in EBVaGC,the relationship between the absence of LMP1 and the lower level of FTase in EBVaGC,the different function of FTase between EBVaGC and EBVnGC ,these all should be studied with more samples in a deep-going way.④Early genes BARF1 and BHRF1 might replace LMP1 to play an important role in the development and progression of EBVaGC.