The Relationship Between Methylation Of FHIT, P16 And Lung Cancer

sLung cancer is a common malignant tumor; its increasing rate is in the first place among all the kind of carcinoma. Because of laking effective early diagnosis methods, the majority of patients with lung cancer present advanced disease. So early finding is very to the lung cancer.Recent study showed that DNA methylation was associated with the development of tumor. The methylation indicated that the - CHS was carried on the cytosine by DNA methyltransferase and turned into 5-mC , which happened the 5'CpG island frequently. The promoter methylation could change the action between protein and DNA, resulting the changing of gene structure and suppressing the gene transcription through multiple ways. There were evidences showed that methylation happened before the tumor. Therefore, the detecting of 5'CpG island methylation was very useful to discover the tumor cell.In 1996, Otha discovered a new tumor suppressor gene -FHIT(Fragile Histidine Traid) by exon-capture technique.Abnormal FHIT has usually been found in various cancers. FHIT gene differs from the classical suppressor gene, abnormalities at transcriptional level were deletion of one or several exons ,sometimes were insertions, but point mutation has been found rarely . So, people has studied the DNA methylationof FHIT in lung cancer speciments .Up to now, the research of the the relationship between the methylation of FHIT and lung cancer is very rarely.P1 6 gene is located at 9p, spans about 40 kb, Including 3exons and two introns. Exons is encoding p1 6 protein, the latter is an inhibitor of cyclin dependent kinase-4 (cdk4). The studies showed that the high methylation of 5'CpG in p1 6 gene promoter had an important function in the occurrence of various tumors .lung cancer tissues samples, surrounding normal and bronchus epithelial squama samples were used in this study to detect FHIT methylation status with the method of MSP and colon in order to illustrate the relationship between the methylation of FHIT with the development of lung cancer, we analyzed the p1 6 methylation status in order to provide useful information for prewarning of lung cancer. Method:1. Samples Collecting: fifty-nine lung cancer samples, thirty surrounding normal lung samples and eleven bronchus epithelial squama samples were collected ,which were used for analysing methylation of these two genes described above.2. Analyse the methylation of the FHIT target genes using MSP.3. The FHIT positive samples were sequenced by clone method and DNAs sequencer.4. Process the data using chi-square test and nonparametric test by meanes of SPSS 10.0 software was processed . The significant level was set atp<0.05.Results:1. The results of FHIT MSP:Among 59 lung cancer tissue, FHIT methylation were found in 22 (38%) samples. In contrast, FHIT methylation were found in only 3(20%)of beside tumor samples in the tissuel and in 0% (0/32) surrounding normal lung tissue. There were significant difference among them (p=0.000). In addition, the significant difference was found between the tissue and normal tissue (p<0.05) ; there was significant difference between the tumors and the tissuel(p<0.05). The methylation were observed in 2(18%)of 11 bronchus epithelial squama samples, and was higher than that of normal lung tissue (p>0.05). No significant difference of FHIT methylation rate between the5smoker and non- smoker(p>0.05). No significant difference were found of between the FHIT methylation rate and the render and histological tissues(p>0.05). 2. The results of p!6 MSP:p1 6 methylation of lung cancer tissue samples, beside tumor samples and surrounding normal lung tissue samples were 5 1 %(33/59), 20%(3/1 5)and 0 % ( 0/32 ) respectivly, the significant difference were observed(p=0.000). In addition there was significant difference between the tumor and normal (p<0.05); the significant difference was found between the group of tumors and the group of beside-tumors(p<0.05). Methylation were found in 2(18%)of 11 bronchus epithel...