| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1999: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Research Abstract |
Frequent allelic imbalances, including loss of heterozygosity (LOH) and microsatellite instability (MSI), have been found on the long arm of chromosome 21 (21q) in several types of human cancer. This study was designed to identify the tumor suppressor locus (or loci) associated with oral squamous cell carcinoma (SCC) on 21q. In order to understand the details of genetic alterations on chromosome 21, we performed polymerase chain reaction analysis of microsatellite polymorphisms corresponding to ten Ioci on this chromosome. We examined forty primary tumor tissues, forty corresponding normal tissues, and seven lymph node metastatic tissues. We identified novel tumor suppressor loci in this region in primary oral SCCs. To further determine the role of 21q deletions in oral cavity carcinogenesis, forty oral SCCs were examined for allelic imbalances (LOH or MSI) at 21q using ten microsatellite markers. Among these forty patients, twenty-six (65%) showed LOH at one or more loci. Deletion mapping of these tumors revealed four discrete, commonly deleted regions on the chromosome arm. Furthermore, we detected MSI in seventeen of those tested cases (42.5%). We compared our results with the clinicopathologic features. A number of sites displaying LOH at 21q could be detected in early stage lesions, and the frequencies of LOH tended to be higher in later clinical stages, but no statistical corrclation was observed. Our results strongly suggest that allelic imbalances on 21q are involved in the development of oral SCC and that at least four different putative tumor suppressor genes contributing to the pathogenesis of this disease are present on 21q. Furthermore, allelic loss on 21q appears to be a useful indicator for evaluating the malignancy and prognosis of oral SCC, because the LOH of recurrent cases was more frequent than that of non-recurrent ones.
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