Korean J Otolaryngol-Head Neck Surg.
2000 Oct;43(10):1094-1101.
Genetic Alterations of Tumor Suppressor Genes in Laryngeal Squamous Cell Carcinoma
- Affiliations
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- 1Department of Otolaryngology, College of Medicine, Ewha Womans University, Seoul, Korea. kim6610@unitel.co.kr
- 2Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul, Korea.
- 3Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Abstract
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BACKGROUND AND OBJECTIVES: Cancer is a genetic disease in which several genetic events are required to induce normal cells to convert to malignancy. Functional loss of tumor suppressor genes is related to these events, but the molecular mechanism is not well known. This study was designed to identify whether the tumor suppressor genes, Fragile Histidine Triad (FHIT), p16, Retinoblastoma (Rb), and p53 were involved in the carcinogenesis of laryngeal squamous cell carcinoma and to determine whether FHIT alterations play a role in laryngeal squamous cell carcinoma.
MATERIALS AND METHOD: The loss of heterozygosity (LOH) was analysed by using microsatellite markers D3S1285 and D3S1481 for FHIT, microsatellite marker D9S171 for p16, investigation of AccII restriction fragment length polymorphism (RFLP) and investigation of variable number of tandem repeat (VNTR) for p53, Xba I RFLP and VNTR for Rb. The FHIT gene was examined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP).
RESULTS
The results of LOH analysis by using microsatellite markers D3S1285 and D3S1481 for FHIT, microsatellite marker D9S171 for p16, investigation of AccII RFLP and investigation of VNTR for p 53, VNTR for Rb were 8% (1/12), 0% (0/13), 18% (2/11), 14% (1/7), 22% (2/9), 17% (1/6), respectively. As a result of analysis of genomic DNA of FHIT gene by SSCP, two cases showed that the polymorphic change occurs at exon 8 codon 98 (CAT-->CAC), and that it is a silent substitution.
CONCLUSION
Based on the experimental result of the change in tumor suppressor genes in laryngeal squamous cell carcinoma, the genetic alterations were most frequently observed in p53 followed by Rb, p16 and FHIT but it is not significant. It is also expected that FHIT has little influence on the process of carcinogenesis of laryngeal squamous cell carcinoma.