The Studies On Molecular Cytogenetic Alterations In Human Lung Carcinomas

Lung cancer is one of the most common cancers in the world, and the incidence is still increasing. Clarification of the molecular cytogenetic mechanisms during the development of lung cancer would be useful for the chemoprevention,early diagnosis and therapy of the deadly human cancer.In this study, we used dual-color FISH, CGH together with Western Blot , PCR, immunohistochemistry analysis to investigate the molecular cytogenetic alterations in the immortalized human bronchial epithelial cell line M , clinic primary human lung cancers and their adjacent normal bronchial epithelium , bronchoscopically obtained specimens. The results were summarized as follows:1. The CGH analysis of cell line M and 10 primary human lung cancers revealed that, in lung cancers, the most common chromosomal alterations involved the gain of 1q, 3q, 7p, 8q, 17q, 20q and the loss of 3p, 4q, 5q, 8p, 10q et al. The frequent alterations of the chromosomal instability may result in the activation of oncogenes and inactivation of tumor suppressor genes located in the different chromosomes.2. In cell line M, we found that the P1 1063(p15/p16) contig had a sequential deletion along with the passages by dual-color FISH. Western blot and immunhistochemistry analysis showed mat the P16 protein had a decreased expression level in the later passages, however, no changes were observed in CDK4 , Cyclin D1 and RB protein expression. The results indicated that the inactivation of p16 gene by deletion is an important factor contributing to the malignant transformation of cell line M.3. In the 41 short-term cultured specimens of human lung cancer and their adjacent bronchial epithelium obtained from 21 cases, we found that in the lung cancer tissues as well as their adjacent bronchial epithelium, the 9p21(P1 1063) had a higher deletion frequency (80.95% and 30% respectively) than that of 3p (CTNNB1)(66.67% and 15% respectively). It showed that the deletion of 9p21(Pl 1063) was probably more important than that of 3p(CTNNB1) in lung carcinogenesis. The bronchoscopically obtained specimens from 14 cases were examined by dual-color FISH. Among 7 specimens which were diagnosed as lung cancer by pathology and/or cytology, 4 cases showed both deletion of 9p(p15/p16)...