Study On HMLH1,p16,FHIT Gene In NSCLC

hMLHI gene, one of the six human mis-match repair(MMR)gene, is a tumor-suppressor gene that locates the region 3p21.3-22. MMR could renovate base mismatch during the DNA replication progress, eliminate the unpaired base sequence because of the genetic recombination among the homologies with the simple repeated order and avoid effectively the production of DNA replication errors (RER). The situation that inactive gene MMR results in the instability of genome, would cause the accumulation unceasingly of the micro-statellite's unsteadiness and the alteration of the related cancer inhibition gene. Finally the cells would cancerate, and the tumor should take shape. As a result, gene hMLHI is related closely to the occurrence of lung cancer.To examine hMLHI gene's LOH> methylation and expression to explore the complete devitalization mechanism of hMLHI gene in abnormal/NSCLC lung tissue,we detected hMLHI gene's LOH (lost of heterozygote) with the way of PCR-Electrophoresed (denatured polyacrylamide gel) -Sliver staining, analyzed the methylation ofhMLHl promoter by restriction endonuclease and specific PCR, detected the exprssion of hMLHl with immunohistochemistry.The experiment divided two groups. One was NSCLC (includes squamous cancer and adenoid), the other was relevant normal lung tissue (6cm away from the tumor).The result showed that the incidence of LOH was 65%. The frequency of LOH was far more higher in the fronter than the latter. The frequency of hMLHl methylation in gastric group was 68%(including 90% exhibiting methylation displayed aberrant hMLHl exprssion).It was proved that the abnormality of hMLHl gene takes effects on carcinogenesis and development of NSCLC. LOH and methylation were mainly the complete devitalization mechanism of hMLHl gene. It is important for the early diagnosis of NSCLC.