Development of Gene diagnosis of Oral-Maxillofacial Deseases by Saliva-derived DNA

唾液DNA诊断口腔颌面部疾病基因的进展

• 批准号: 13557177
• 负责人: OKAMOTO Tetsuji
• 金额: $ 9.02万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557177/
• 关键词: FGFRs; patched; EXT1, 2; Tie-2; Gene Diagnosis; Craniosyostosis; venous malformations; nevoid basal cell carcinoma syndrome; 頭蓋早期癒合症(FGFR1,FGFR2); 外骨症(EXT1、EXT2)

Mutations in receptors have been linked to an increasing number of inherited human disease syndromes affecting oral-craniofacial functions. Both gain-of-function mutations resulting in constitutive receptor activation, and loss-of-function mutations resulting in non-functional or dominant negative receptors, have been observed.In the present study, we have analyzed the mutations of receptor families (patched ; a receptor for the hedgehog protein, fibroblast growth factor receptor (FGFR)-1, -2, -3, Tie-2 ; an endothelial cell-specific receptor tyrosine kinase) that are involved in inherited syndromes (nevoid basal cell carcinoma syndrome ; NBCCS/Gorlin Syndrome, craniosynostosis, achondroplasia, oral cancers and venous malformations, respectively) by both PCR-SSCP and direct sequencing of the DNA derived from peripheral blood lymphocytes and saliva, to examine the phenotype/genotype correlations in patients with the syndromes. In addition, we have studied cellular growth, differentiation and intracellular signal transduction pathways in the target cells expressing mutated genes to elucidate the molecular function of the mutated receptor genes in the syndromes.We describes the molecular consequences of the disease mutations, and predicts that many novel mutations remain to be identified.

受体的突变与越来越多的影响口颅面功能的遗传性人类疾病综合征有关。已观察到导致组成性受体激活的功能获得突变和导致无功能或显性负性受体的功能丧失突变。在本研究中，我们分析了受体家族的突变（补丁;刺猬蛋白的受体，成纤维细胞生长因子受体（FGFR）-1、-2、-3、Tie-2 ;一种内皮细胞特异性受体酪氨酸激酶），其与遗传综合征有关（痣样基底细胞癌综合征; NBCCS/Gorlin综合征、颅缝早闭、软骨发育不全、口腔癌和静脉畸形，分别采用PCR-SSCP和直接测序的方法，检测患者外周血淋巴细胞和唾液DNA的表型/基因型相关性。此外，我们还研究了表达突变基因的靶细胞的细胞生长、分化和细胞内信号转导途径，以阐明突变受体基因在综合征中的分子功能，描述了疾病突变的分子后果，并预测仍有许多新的突变有待鉴定。

项目成果

Koike, C., Michimukai, E., Kitamira, N., Okamoto, T., Iba, H.: "Introduction of wild-type patched gene suppresses the oncogenic potential of human squamous cell carcinoma cell lines including A431"Oncogene. 21. 2670-2678 (2002)

Koike, C.、Michimukai, E.、Kitamira, N.、Okamoto, T.、Iba, H.：“引入野生型修补基因可抑制包括 A431 在内的人鳞状细胞癌细胞系的致癌潜力”癌基因。

Sato, J.D., Okamoto, T., et al.: "Basic Animal Cell Culture(J. M. Davis ; editor, 2nd Edition):"Oxford Univ. Press, Oxford, England,. 381 (2001)

Sato, J.D.、Okamoto, T. 等人：“基础动物细胞培养（J. M. Davis；编辑，第二版）：”牛津大学。

Asada, N., Y.Tanaka, M.Kitamoto, T.Nakanishi, G.Kajiyama, K.Chayama, T.Okamoto: "Expression of fibroblast growth factor (FGF) receptor genes in human hepatoma-derived cell lines"In Vitro Cellular Developmental Biology. (印刷中). (2003)

Asada, N., Y.Tanaka, M.Kitamoto, T.Nakanishi, G.Kajiyama, K.Chayama, T.Okamoto：“成纤维细胞生长因子 (FGF) 受体基因在人肝癌衍生细胞系中的表达”体外细胞发育生物学（正在出版）（2003）。

Ojikja, M., Islam Kamrul, Shintani, T., Zhang, Y. Okamoto, T., Sakagami, Y.: "CytotoxicAcylspermidines from a Soft Coral : Three New Cytotoxic Acylspermidines from a Soft Coral, Sinularia sp"Biosci. Biotechnol. Biochem.. in press. (2003)

Ojikja，M.，Islam Kamrul，Shintani，T.，Zhang，Y. Okamoto，T.，Sakagami，Y.：“来自软珊瑚的细胞毒性酰基亚精胺：来自软珊瑚的三种新的细胞毒性酰亚精胺”Biosci。

Asada, N., Y. Tanaka, T. Okamoto., et al.: "Expression of FGF receptor genes in human hepatoma-derived cell lines"In Vitro Cellular Developmental Biology. in press. (2003)

Asada, N., Y. Tanaka, T. Okamoto., et al.：“FGF 受体基因在人肝癌衍生细胞系中的表达”体外细胞发育生物学。