MICROSATELLITE INSTABILITY AND LOSS OF HETEROZYGOSITY AT CHROMOSOME-9AND CHROMOSOME-17 IN NONSMALL CELL LUNG-CANCER

Background: Microsatellite instability (MI) and loss of heterozygosity (LOH) are described in lung cancer specimens. However, their importan ce in tumorigenesis remains unknown. The aim of this study was to iden tify the presence of MI and LOH in human tumor and normal bronchial mu cosa DNA. Methods: We performed biopsies with fiberoptic bronchoscopy and took specimens from the tumor and from the opposite site normal br onchial mucosa in 20 patients with non-small-cell lung cancer (NSCLC). Four patients had an adenocarcinoma, while 16 had a squamous cell car cinoma. Also, 6 patients had an early-stage disease (stages I and II), while 14 patients had an advanced-stage disease (stages III and IV). All paired specimens were studied for MI and LOH on chromosome 17p, 17 q, 9p, and 9q, with 10 polymorphic markers. Results: Sixteen of 20 tum ors displayed genetic alterations (80%). Six tumors (30%) exhibited MI , five tumors (25%) exhibited LOH, while five tumors exhibited MI and LOH concurrently. The marker HBX had the most frequent incidence of LO H (4/20, 20%), indicating that the hbx gene becomes a strong candidate tumor suppressor gene, whereas of MI it was D17S515 (4/20, 20%). No r elationship was observed between the presence of LOH or MI and the his tologic subtype of NSCLC or the stage of the disease. Conclusion: Resu lts suggest that genetic alterations el;ist in tumor, compared with th e normal mucosa DNA. They may have a role in carcinogenesis as they ex ist in all stages and in both NSCLC histologic subtypes studied.