EXPLOITATION OF NEW DIAGNO-THERAPEUTIC PROCEDURES OF HUMAN ENDOCERVICAL ADENOCARCINOMA OF THE UTERUS BASED ON CYTOGENETIC MECHANISMS OF MULTI- STEP CARCINOGENESIS

基于多步癌变细胞遗传学机制的人类子宫内膜腺癌诊断治疗新流程的开发

• 批准号: 12671643
• 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: 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-12671643/
• 关键词: ENDOCERVICAL ADENQCARCINOMAS; TGF 13 RII; BAX; CHROMOSOMAL IMBALANCE; PTEN; MICROSATELLITE INSTABILITY; COMPARATIVE GENOMIC INSTABILITY; MULTISTEP CARCINOGENESIS; 子宮頚部腺癌; TGFβRII; BAX; SMAD; CGH; 発癌過程

We analysed the mutational status of the TGF β RII, BAX, and PTEN/MMAC1 genes as well as microsatellite instability (MI) in consecutive cases of endocervical adenocarcinoma 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 genornic hybridization (CGH) analysis. CGH analysis may provides a genome-wide overview about tumor-associated genomic imbalances. Among the tumors, a few showed, the MI+ phenotype. Also, few tumors demonstrated a significant mutation with a definite amino acid change in PTEN/MMAC1 gene. CGH analysis demonstrated that a few tumors showed chromosomal copy number losses and/or amplifications, whereas there are no common chromosomal foci showing losses or amplifications among the tumors analysed so far. The role of TGF β RI and BAX genes may be limited as a target gene of MI+ phenotype in endocervical adenocarcinoma, because only a few tumors demonstrated MI+ phenotype in these tumors.Additional explorations are needed to elucidate the cytogenetic mechanisms of multistep carcinogenesis in endocervical adenocarcinomas of the uterus.

我们分析了在我们研究所进行手术的子宫颈内腺癌的连续病例中TGF β RII、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，我们使用比较基因组杂交（CGH）分析。CGH分析可以提供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。此外，少数肿瘤表现出显着的突变与明确的氨基酸变化的PTEN/MMAC 1基因。CGH分析表明，少数肿瘤显示染色体拷贝数丢失和/或扩增，而到目前为止，在分析的肿瘤中没有常见的染色体病灶显示丢失或扩增。TGF β RI和BAX基因作为MI+表型靶基因的作用可能有限，因为只有少数肿瘤表现出MI+表型，因此需要进一步探讨子宫颈内腺癌多步骤癌变的细胞遗传学机制。

项目成果

Sugiyama Y, Hirai Y: "Microdissection is essential for gene expression profiling of clinically resected cancer tissues"Am J Clin Pathol. 117. 109-116 (2001)

Sugiyama Y、Hirai Y：“显微解剖对于临床切除的癌症组织的基因表达谱分析至关重要”Am J Clin Pathol。

Hirai Y, Takeshima N, Kato T, Hasumi K.: "Malignant potential of positive peritoneal cytology in endometrial cancer."Obstet Gynecol. 97(5 Pt 1). 725-8 (2001)

Hirai Y、Takeshima N、Kato T、Hasumi K.：“子宫内膜癌腹膜细胞学阳性的恶性潜力。”Obstet Gynecol。

Hirai Y: "Somatic mutations of the PThN/NMAC1 gene associated with frequent chromosomal loss detected using comparative genomic hybridization in endometrial cancer"Gynecol Oncol. 83. 81-8 (2001)

Hirai Y：“使用比较基因组杂交在子宫内膜癌中检测到与频繁染色体丢失相关的 PThN/NMAC1 基因体细胞突变”Gynecol Oncol。

Sekine M, Hiral Y: "Mutational analysis of brcal and brca2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families"Clin Cancer Res. 7. 3144-3150 (2001)

Sekine M、Hiral Y：“82 个卵巢癌家族的 brcal 和 brca2 突变分析及卵巢癌临床病理分析”Clin Cancer Res。

Hirai Y, Tanaka N, Furuta R, Kawaguchi T, Sakamoot M, Shirahatma S, Noda T.: "Somatic mutations of the PTEN/NMAC1 gene associated with frequent chromosomal loss detected using comparative genomic hybridization in endometrial cancer"Gynecol Oncol. 83(1). 8

Hirai Y、Tanaka N、Furuta R、Kawaguchi T、Sakamoot M、Shirahatma S、Noda T.：“使用子宫内膜癌比较基因组杂交检测到与频繁染色体丢失相关的 PTEN/NMAC1 基因体细胞突变”Gynecol Oncol。