Objective: To investigate the allelic loss of heterozygosity in three tumor suppressor genes, Fhit, hMLH1 and VHL, located at three corresponding regions 3p14-cen, 3p21.3-22 and 3p25-26 with a high fregnency in lung cancer and to evaluate the expression of Fhit protein in the tumor tissue of lung cancer.
Methods: Microsatellite analysis was performed by using the primers that amplified polymorphic sequences inside or flanking to the three genes in the tumor tissues collected from 45 cases of primary lung cancer. Immunohistochemical staining was performed to detect the expression of Fhit protein in the tumor tissues from 17 out of the 45 cases.
Results: For loci D3S1234, D3S1300 and D3S4103 that are located in the intron of Fhit gene, LOH was found in informative cases as 62.9%, 63.6% and 59.5%, respectively. In D3S1561 and D3S1612 that are linked with hMLH1 gene, LOH was detected in 54.5% and 63.2% of informative cases, respectively. LOH was found in 64.3% and 41.7% of informative cases, at D3S1038 and D3S1283, respectively, which are flanked to VHL gene. Expression of Fhit protein was down regulated in tumor tissues of 11 out of 17 cases (64.7%); among 10 of the 11 samples, LOH was detected at one or more of the microsatellite loci tested.
Conclusion: High frequency loss of one allele in tumor suppressor genes Fhit, hMLH1 and VHL was observed in the tumor tissues of lung cancer, indicating that it may play a role in carcinogenesis of human lung, and may provide some new approaches to early gene detection for lung cancer. Loss of one allele of Fhit gene may be one of the mechanisms for down regulation of Fhit protein expression in lung cancer.