2001 Fiscal Year Final Research Report Summary
Mutational events of p53 gene in salivary gland tumors
| Project/Area Number |
12671766
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | Niigata University |
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Principal Investigator |
CHENG Jun Graduate School of Medical and Dental Sciences, Niigata University, Associate Professor, 大学院・医歯学総合研究科, 助教授 (40207460)
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| Co-Investigator(Kenkyū-buntansha) |
IDA-YONEMOCHI Hiroko Graduate School of Medical and Dental Sciences, Niigata University, Assistant, 大学院・医歯学総合研究科, 助手 (60293213)
SAKU Takashi Graduate School of Medical and Dental Sciences, Niigata University, Professor, 大学院・医歯学総合研究科, 教授 (40145264)
OHSHIRO Kazufumi Graduate School of Medical and Dental Sciences, Niigata University, Assistant, 大学院・医歯学総合研究科, 助手 (50332648)
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| Project Period (FY) |
2000 – 2001
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| Keywords | salivary gland tumor / p53 / cancer suppressor gene / gene mutation / DNA / PCR / sequecing / SSCP |
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| Research Abstract |
In order to determine mutational events of the p53 tumor suppressor gene in salivary gland tumors, 117 cases of surgical materials of salivary tumors were analyzed by a direct sequencing of PCR products of DNA samples extracted from formalin-fixed paraffin-embedded tissue sections. The samples included 35 cases of lymphoepithelioma, 30 of mucoepidermoid carcinoma, 33 of Warthin tumor and 19 of pleomorphic adenoma. At the same time, cultured cells of adenoid cystic carcinoma were also examined.
Lymphoepithelioma is an undifferentiated carcinoma with the lymphoid stroma and associated with the Epstein-Barr virus infection. The pathogeneses of mucoepidermoid carcinomas and Warthin tumors have been related to the exposure to ionizing radiation by atomic bomb in Hiroshima and Nagasaki. However, nothing is known about the pathogenesis for other types of salivary gland tumor. The investigation was performed in the background of the so far accumulated information.
In this study we first examined
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exons 5-7 of p53 gene with PCR-fluoro-SSCP and then cases with abnormal SSCP profiles were subjected to direct sequencing. The results were compared with immunohistochemical staining patterns for p53 protein. Most conspicuous mutational events of p53 gens were found in exons 5-7 of lymphoepitheliomas, which instead showed scarce p53 protein immunopositivity. These mutational points were highly common among the cases examined. In contrast, no apparent mutational events were detected in pleomorphic adenomas, even in those with atypical cells that showed strong immunoreactions for p53 gene products. Warthin tumors and mucoepidermoid carcinomas often showed several point mutations in exons 5 and 7, which did not effect on amino acid translation so much, which seemed to be resulted from genetic polymorphism of the gene. However, these point mutations were shared by many cases of malignant and benign salivary gland tumors.
These results suggest that the specific point mutations in exons 5 and 7 of the p53 gene found in the present study are important genetic background for salivary gland tumorigenesis. Less
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