EXPLOITATION OF NEW DIAGNO-THERAPEUTIC PROCEDURES OF HUMAN UTERINE ENDOCERVICAL AND ENDOMETRIAL ADENOCARCINOMAS BASED ON CYTOGENETIC STUDY OF MULTI- STEP CARCINOGENESIS

基于多步致癌作用的细胞遗传学研究开发人类子宫内膜癌和子宫内膜腺癌的新诊断治疗方法

• 批准号: 14571599
• 负责人: HIRAI Yasuo
• 金额: $ 2.18万
• 依托单位: Japanese Foundation For Cancer Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571599/
• 关键词: ENDOCERVICAL ADENOCARCINOMAS; ENDOMETRIAL ADENOCARCINOMA; GLASSY CELL CARCINOMA; CONVENTIONAL CGH; ARRAY-BASED CGH; MICROSATELLITE INSTABILITY; PTEN; HPV INFECTION; 子宮頸部腺癌; HPV感染; TCFβ typeII Receptor; TCF βtype II Recetpor

We analyzed the mutational status of the TGF βRII, BAX, and PTEN/MMAC1 genes as well as microsatellite instability (MI) in consecutive cases of endocervical and endometrial adenocarcinomas of the uterus operated on at our Institute. To examine copy number losses and/or amplifications at the chromosomal region bearing all the genes, we used comparative genomic hybridization (CGH) analysis (both conventional and array-based). CGH analysis provides a genome-wide overview about tumor-associated genomic imbalances. Among the tumors, a few showed the MI+ phenotype in endocervical adenocarcinoma. Also, few tumors demonstrated a significant mutation with a definite amino acid change in PTEN/MMAC1 gene, which is prominent in endometrial adenocarcinoma. CGH analysis demonstrated several promising oncogenes which may have a role in multi-step carcinogenesis of uterine endocervical and endometrial adenocarcinomas.Additional explorations are needed to elucidate the cytogenetic mechanisms of multi- step carcinogenesis in endocervical and endometrial adenocarcinomas of the uterus.

我们分析了在我们研究所进行手术的子宫颈内和子宫内膜腺癌的连续病例中TGF βRII、BAX和PTEN/MMAC 1基因的突变状态以及微卫星不稳定性（MI）。为了检查携带所有基因的染色体区域的拷贝数损失和/或扩增，我们使用了比较基因组杂交（CGH）分析（常规和基于阵列的）。CGH分析提供了关于肿瘤相关基因组失衡的全基因组概述。在肿瘤中，少数显示MI+表型的宫颈腺癌。此外，很少有肿瘤表现出显着的突变，明确的氨基酸变化，在PTEN/MMAC 1基因，这是突出的子宫内膜腺癌。CGH分析显示了几个有希望的癌基因，它们可能在子宫颈和子宫内膜腺癌的多步癌变过程中起作用，但需要进一步的探索来阐明子宫颈和子宫内膜腺癌多步癌变的细胞遗传学机制。

项目成果

A large-scale gene expression comparison of microdissected small-sized endometrial cancers with or without hyperplasia matched to same-patient normal tissue.

对显微解剖的小尺寸子宫内膜癌（伴或不伴增生）与同一患者正常组织进行大规模基因表达比较。

• 发表时间: 2003
• 期刊: Clin Cancer Res 9
• 作者: Sugiyama;Y.;et al.
• 通讯作者: et al.

Sugiyama Y, Hirai Y, et al.: "A large-scale gene expression comparison of microdissected, small-sized endometrial cancers with or without hyperplasia matched to same-patient normal tissue."Clin Cancer Res.. 15. 5589-5600 (2003)

Sugiyama Y、Hirai Y 等人：“对有或没有增生的显微解剖小尺寸子宫内膜癌与同一患者正常组织相匹配的大规模基因表达比较。”Clin Cancer Res.. 15. 5589-5600 (

Tabata T, Hirai Y, et al.: "A randomized study or primary bleomycin, vincristine, mitornycin and cisplatin(BOMP) chemotherapy followed by radiotherapy versus radiotherapy alone in stage IIIB and IVA squamous cell carcinoma of the cervix."Anticancer Res..

Tabata T、Hirai Y 等人：“针对 IIIB 期和 IVA 期宫颈鳞状细胞癌进行原发博来霉素、长春新碱、丝裂霉素和顺铂 (BOMP) 化疗后放疗与单独放疗的随机研究。”Anticancer Res..

Conventional and array-based comparative genomic hybridization analyzes of novel cell lines harboring HPV18 from glassy cell carcinoma of the uterine cervix.

对来自宫颈玻璃细胞癌的携带 HPV18 的新型细胞系进行常规和基于芯片的比较基因组杂交分析。

• 发表时间: 2004
• 期刊: Int J Oncol. Apr;24(4)
• 作者: Hirai Y;Kawamata Y;Takeshima N;Furuta R;Kitagawa T;Kawaguchi T;Hasumi K;Sugai S;Noda T.
• 通讯作者: Noda T.

Putative gene loci associated with carciongenesis and metastasis of endocervical adenocarcinomas of uterus determined by conventional and array-based CGH

通过常规和基于芯片的 CGH 确定与子宫宫颈内膜腺癌发生和转移相关的推定基因位点

• 发表时间: 2004
• 期刊: Am J Obstet Gynecol 191
• 作者: Hirai Y