Molecular pathological study of mechanism in malignant changes of oral benign tumors

口腔良性肿瘤恶变机制的分子病理学研究

• 批准号: 16591821
• 负责人: CHENG Jun
• 金额: $ 2.3万
• 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: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591821/
• 关键词: pleomorphic adenoma; salivary gland tumor; melanotic neuroectodermal tumor; karyotyping analyses; mutation of oncogene; DNA tip; DNA sequencing; capsular invasion; 唾液腺多形性腺腫; 脈管侵襲; 染色体転座; 低酸素; VEGF; 顎骨石灰化歯原性曩胞; 細胞培養; がん関連遺伝子; 遺伝子変異; RT-PCR

This research project was carried out in order to study a possible molecular pathway of malignant transformation of oral benign tumors. We mainly focus on salivary pleomorphic adenoma, because we had already proposed a possibility of malignant changes of atypical tumor cells or focal carcinomas within pleomorphic adenomas. To this end, we have isolated six cell systems (designated SMAP1 to SMAP6) from a benign pleomorphic adenoma of the parotid gland of a 61 year-old female. SMAP1/3 showed duct epithelial characteristics with polygonal cell shapes, while SMAP4/6 were spindle-shaped with some myoepithelial cell differentiation. Chromosome analyses showed the cells had not only numeral abnormalities such as 5n ploidies with average numbers of 107 chromosomes but also various kinds of structural abnormalities, such as deletions, translocations, derivatives and isodicentric chromosomes. Among them, der(9)t(9; 13)(p13.3;q12.3) was shared by all of the six cell systems. In addition, they all … More had a common deletion of the last base G of codon 249 (AGG to AG_) of the p53 gene, which would result in generation of its nonsense gene product. The findings suggest that pleomorphic adenoma contains tumor cells which are precancerous and are able to transform into malignant with above mentioned gene alterations, and the present study is the first in-vitro demonstration that carcinomas can arise secondarily from adenomas in the salivary gland.In addition to such gene alterations, there were some other biological characteristics to pleomorphic adenomas. They were capsular and vascular invasions. Their frequency was 100% (extracapular 20%) and 15%, respectively, when examined histopathologically in 104 surgical specimens. In the sites with capsular or vascular invasions, the stroma was myxoid and poorly vascularized. This histology was explained by VEGF and HIF-1a expression modes, which were hypoxia-related. In cells established from a melanotic neuroectodermal tumor of infancy, there was the same chromosome alteration found in SMAP cells, and this translocation will be worthwhile to be investigated further for the molecular mechanism of secondary malignant changes of benign tumors. Less

本研究项目旨在研究口腔良性肿瘤恶变的可能分子途径。我们主要关注唾液腺多形性腺瘤，因为我们已经提出了多形性腺瘤内非典型肿瘤细胞或局灶性癌发生恶变的可能性。为此，我们从一名 61 岁女性腮腺良性多形性腺瘤中分离出 6 个细胞系统（指定为 SMAP1 至 SMAP6）。 SMAP1/3显示导管上皮特征，细胞形状为多边形，而SMAP4/6呈纺锤形，有一些肌上皮细胞分化。染色体分析显示，这些细胞不仅存在平均107条染色体的5n倍体等数量异常，而且还存在缺失、易位、衍生物和等双着丝粒染色体等多种结构异常。其中，der(9)t(9; 13)(p13.3;q12.3) 为所有六个细胞系统所共享。此外，它们都共同删除了 p53 基因密码子 249 的最后一个碱基 G（AGG 到 AG_），这将导致其无义基因产物的产生。研究结果表明，多形性腺瘤含有癌前肿瘤细胞，并且能够通过上述基因改变转化为恶性细胞，本研究首次在体外证明唾液腺腺瘤可以继发癌。除了这种基因改变外，多形性腺瘤还有一些其他生物学特征。它们是包膜和血管侵犯。当对 104 个手术标本进行组织病理学检查时，它们的频率分别为 100%（囊外 20%）和 15%。在有包膜或血管侵犯的部位，间质呈粘液样且血管化不良。这种组织学可以通过与缺氧相关的 VEGF 和 HIF-1a 表达模式来解释。在婴儿黑色素神经外胚层肿瘤建立的细胞中，在SMAP细胞中也发现了相同的染色体改变，这种易位对于良性肿瘤继发恶变的分子机制值得进一步研究。较少的

项目成果

口蓋腫瘍

腭肿瘤

• 发表时间: 2013
• 作者: 程 クン;丸山 智;阿部達也, 山崎 学;朔 敬
• 通讯作者: 朔 敬

Calcification and ghost cell differentiation in calcifying odontogenic cyst cell systems

钙化牙源性囊肿细胞系统中的钙化和影细胞分化

• 发表时间: 2004
• 期刊: J Oral Pathol Med 33(8)
• 作者: 丸川征四郎;小谷穣治;Swelam W;Jen KY;Cheng J
• 通讯作者: Cheng J

Nucleotide sequences and functions of the Epstein-Barr virus latent membrane protein 1 genes isolated from salivary gland lymphoepithelial carcinomas

从唾液腺淋巴上皮癌中分离出的 Epstein-Barr 病毒潜伏膜蛋白 1 基因的核苷酸序列和功能

• 发表时间: 2005
• 期刊: Virus Genes 30(2)
• 作者: Masahiro Morita;Toru Suzuki;Kentaro Ito;Tadashi Yamamoto;Hall WW;Niinuma A;Tsubata C;Higuchi M;Kawakami H;Jen KY
• 通讯作者: Jen KY

Calcification and ghost cell differentiation in calcifying odontogenic cyst cell systems.

钙化牙源性囊肿细胞系统中的钙化和影细胞分化。

• 发表时间: 2004
• 期刊: Journal of Oral Pathology and Medicine 33(8)
• 作者: Cheng J;Maruyama S;Suzuki M;Fujita H;Takagi R;Saku T
• 通讯作者: Saku T

舌腫瘍

舌肿瘤

• 发表时间: 2005
• 期刊: 日本病理学会東北支部学術集会抄録集症例データベース http://www.jsptn.mcpu.jp/index.html
• 作者: Jen KY;Higuchi M;Cheng J;Li J;Wu LY;Li YF;Lin HL;Chen Z;Gurtsevitch V;Fujii M;Saku T;Goshima M;宇佐美真;程 くん
• 通讯作者: 程 くん