Genetic Alterations of Human Oral Cancers Using Comparative Genomic Hybridization

ABSTRACT

The development and progression of oral cancer is associated with an accumulation of multiple genetic alterations through the multistep processes. Comparative genomic hybridization(CGH), newly developed cytogenetic and molecular biologic technique, has been widely accepted as a useful method to allow the detection of genetic imbalance in solid tumors and the screening for chromosome sites frequently affected by gains or losses in DNA copy number. The authors examined 19 primary oral squamous cell carcinomas using CGH to identify altered chromosome regions that might contain novel oncogenes and tumor suppressor genes. Interrelationship between these genetic aberrations detected and major oncogenes and tumor suppressor genes previously recognized in carcinogenesis of oral cancers was studied. 1. Changes in DNA copy number were detected in 14 of 19 oral cancers (78.9%, mean: 5.58, range: 3~13). High level amplification was present in 4 cases at 9p23, 12p21.1~q13.1, 3q and 8q24~24.3. Fourteen cases(78.9%, mean: 3.00, range: 1~8) showed gains of DNA copy number and 12 cases(70.5%, mean: 2.58, range: 1~9) revealed losses of DNA copy number. 2. The most common gains were detected on 3q(52.6%), 5p(21.0%), 8q(21.0%), 9p(21.0%), and 11q(21.0%). The losses of DNA copy number were frequently occurred at 9p(36.8%), 17q(36.8%), 13q(26.3%), 4p(21.0%) and 9p(21.0%). 3. The minimal common regions of gains were repeatedly observed at 3q24~26.7, 3q27~29, 1q22~31, 5p12~13.3, 8q23~24, and 11q13.1-13.3. The minimal common regions of losses were detected at 9q11~21.3, 17p31, 13q22~34, and 14p16. 4. In comparison of CGH results with tumor stages, the lower stage group showed more frequent gain at 3q, 5q, 9p, and 14q, whereas gains at 1q(1q22~31) and 11q(11q13.1~13.3) were mainly detected in higher stage group. The loss at 13q22~34 was exclusively detected in higher stage. The results indicate that the most frequent genetic alterations in the development of oral cancers were gains at 3q24~26.3, 1q22~31, and 5p12~13.3 and losses at 9q11~21.3, 17p31, and 13q. It is suggested that genetic alterations manifested as gains at 3q24~26.3, 3q27~29, 5p12~13.3 and 5p are associated with the early progression of oral cancer. Gains at 1q22~31 and 11q13.1~13.3 and loss at 13q22-34 could be involved in the late progression of oral cancers.