Mutational events of p53 gene in salivary gland tumors

唾液腺肿瘤中p53基因的突变事件

• 批准号: 12671766
• 负责人: CHENG Jun
• 金额: $ 2.24万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671766/
• 关键词: salivary gland tumor; p53; cancer suppressor gene; gene mutation; DNA; PCR; sequecing; SSCP; 血管分布

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 … More 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

为了确定涎腺肿瘤中p53抑癌基因的突变事件，通过对从福尔马林固定的石蜡包埋的组织切片中提取的DNA样品的PCR产物直接测序来分析117例涎腺肿瘤的手术材料。其中淋巴上皮瘤35例，粘液表皮样癌30例，Warthin瘤33例，多形性腺瘤19例。腺样囊性癌是一种具有淋巴样间质的未分化癌，与EB病毒感染有关。在广岛和长崎，粘液表皮样癌和Warthin瘤的发病与原子弹的电离辐射照射有关。然而，对于其他类型的涎腺肿瘤的发病机制尚不清楚。本研究是在迄今为止积累的信息的背景下进行的。 ...更多信息 应用PCR-fluoro-SSCP技术对p53基因第5-7外显子进行扩增，并对SSCP异常者进行直接测序。结果与p53蛋白免疫组化染色模式进行了比较。淋巴上皮瘤中p53基因的最显著突变事件出现在外显子5-7，而p53蛋白的免疫阳性率很低。这些突变点在检查的病例中非常常见。相反，在多形性腺瘤中没有检测到明显的突变事件，即使在那些具有非典型细胞的肿瘤中也没有检测到p53基因产物的强烈免疫反应。Warthin瘤和粘液表皮样癌常在第5和第7外显子出现多个点突变，但对氨基酸翻译的影响不大，这可能是该基因的遗传多态性所致。但这些点突变在许多涎腺良恶性肿瘤中存在，提示本研究中发现的p53基因第5、7外显子的特异性点突变是涎腺肿瘤发生的重要遗传背景。少

项目成果

Cheng J: "Biological background for differential diagnosis of salivary pleomorphic adenoma from myoepithelioma by CT images and characteristic histopathology of paucivascular stroma"2^<nd> International Symposium of Molecular Pathology, Chengdu, China, Au

程J：“通过CT图像和少血管基质的特征性组织病理学鉴别唾液多形性腺瘤与肌上皮瘤的生物学背景”2^<nd>国际分子病理学研讨会，成都，中国，Au

Cheng J, Maruyama S, Hayashi T, Wu L, Zhou Z and Saku T: "Biological background for differential diagnosis of salivary pleomorphic adenoma from myoepithelioma by CT images and characteristic histopathology of paucivascular stroma"2^<nd> International Symp

Cheng J、Maruyama S、Hayashi T、Wu L、Zhou Z 和 Saku T：“通过 CT 图像和少血管基质的特征性组织病理学鉴别唾液腺多形性腺瘤与肌上皮瘤的生物学背景”2^<nd> 国际症状

Maruyama S: "Sebaceous lymphoadenoma of the lip"J Oral Pathol Med. 31(4). 242-243 (2002)

Maruyama S：“唇部皮脂腺淋巴腺瘤”J Oral Pathol Med。

Cheng J, Abe M, Saku T: "p53 mutations in salivary gland tumors"5^<th> Joint Conference of the American Association for Cancer Research and the Japanese Cancer Association, Maui, Hawaii, Feb. 12-16, Abstract. 9 (2001)

Cheng J、Abe M、Saku T：“唾液腺肿瘤中的 p53 突变”美国癌症研究协会和日本癌症协会第 5 届联合会议，夏威夷毛伊岛，2 月 12-16 日，摘要。

Cheng, J. et al.: "Vascular distribution of salivary gland tumors refleted into their histology"First International Congress on Salivary Gland Diseases. (Abstract). 90 (2002)

Cheng, J. 等人：“唾液腺肿瘤的血管分布反映到其组织学中”第一届国际唾液腺疾病大会。