EXLPLOITATION OF NEW DIAGNOSTIC PROCEDURES OF HUMAN ENDOMETRIAL CANCERS IN RELATION TO CYTOGENETIC MECHANISMS OF MULTI-STEP CARCINOGENESIS ELUCIDATED WITH CGH

与 CGH 阐明的多步癌变细胞遗传学机制相关的人类子宫内膜癌新诊断程序的开发

• 批准号: 09671726
• 负责人: HIRAI Yasuo
• 金额: $ 1.41万
• 依托单位: JAPANESE FOUNDATION OF 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: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671726/
• 关键词: ENDOMETRIAL CARCINOMA; TGFβRII; BAX; β-catenin; PTEN; MICROSATELLITE INSTABILITY; COMPARATIVE GENOMIC INSTABILITY; MULTISTEP CARCINOGENESIS; TGFβRII; CGH(comparative genomic hybridisation); TGF β Rll; E2F; 臨床病理学; 多段階発癌; エストロゲンリセプター; CGH

We analyzed the mutational status of the TGFβRII, BAX, and PTEN/MMAC1 genes as well as microsatellite instability (MI) in 29 consecutive cases of endometrial carcinoma operated on at our Institute. To examine copy number loss at the chromosomal regions bearing these genes, we used comparative genomic hybridization (CGH) analysis. CGH analysis may provides a genome-wide overview about tumor-associated genomic imbalances. Among nine tumors that showed the MI+ phenotype, four (44%) demonstrated a significant mutation with a definite amino acid change in PTEN/MMAC1 gene. CGH analysis demonstrated that all the four tumors (100%) showed chromosomal copy number loss around the locus of this gene, whereas four (57%) of seven tumors with PTEN/MMAC1 mutations showed chromosomal loss or double mutations in MI- carcinomas. The role of TGFβRII and BAX genes is limited as a target gene of MI+ phenotype in endometrial cancer, because several mutations of these genes were detected but a chromosomal loss was demonstrated by CGH in only one tumor in MI+ endometrial cancers with mutation. According to CGH results, chromosomal imbalances were demonstrated at 1q, 9q, 2q, 12q. Frequent abnormal cytoplasmic/ nuclear accumulation of β-catenin was observed in this endometrial series.

我们分析了我所连续 29 例子宫内膜癌手术中的 TGFβRII、BAX 和 PTEN/MMAC1 基因的突变状态以及微卫星不稳定性 (MI)。为了检查携带这些基因的染色体区域的拷贝数丢失，我们使用了比较基因组杂交（CGH）分析。 CGH 分析可以提供有关肿瘤相关基因组失衡的全基因组概述。在显示 MI+ 表型的 9 个肿瘤中，有 4 个 (44%) 表现出 PTEN/MMAC1 基因中存在明确氨基酸变化的显着突变。 CGH 分析表明，所有 4 个肿瘤 (100%) 均显示该基因位点周围的染色体拷贝数丢失，而 7 个具有 PTEN/MMAC1 突变的肿瘤中有 4 个 (57%) 在 MI 癌​​中显示染色体丢失或双突变。 TGFβRII和BAX基因作为子宫内膜癌中MI+表型的靶基因的作用受到限制，因为检测到这些基因的多个突变，但CGH仅在具有突变的MI+子宫内膜癌中的一个肿瘤中证明了染色体丢失。根据CGH结果，1q、9q、2q、12q出现染色体失衡。在此子宫内膜系列中观察到β-连环蛋白频繁异常细胞质/核积聚。

项目成果

H Yoshikawa, C Nagata, K Noda, S Nozawa, A Yajima, S Sekiya, H Sugimori, Y Hirai, K Kanazawa, M Sugase, H Shimizu, T Kawana: "Human papillomavirus infection and other risk factors for cervical intraepithelial neoplasia in Japan"British Journal of Cancer.

H Yoshikawa、C Nagata、K Noda、S Nozawa、A Yajima、S Sekiya、H Sugimori、Y Hirai、K Kanazawa、M Sugase、H Shimizu、T Kawana：“日本人乳头瘤病毒感染和宫颈上皮内瘤变的其他危险因素

Kenji Yanoh, Nobuhiro Takeshima, Yasuo Hirai, Atuko Minami, Nagayasu Toyoda, Katsuhiko Hasumi: "Morphologic analysis of positive peritoneal cytology in endometrial carcinoma"Acta Cytologica. 43. 814-819 (1999)

Kenji Yanoh、Nobuhiro Takeshima、Yasuo Hirai、Atuko Minami、Nagayasu Toyoda、Katsuhiko Hasumi：“子宫内膜癌腹膜细胞学阳性的形态学分析”Acta Cytologica。

竹島信宏、平井康夫他: "子宮頚癌la期(新規約)の臨床的取り扱いについて-新FlGOla期子宮頚部扁平上皮癌の取り扱いについて-" 第37回子宮癌研究会記録(子宮癌研究会編). 38-43 (1999)

Nobuhiro Takeshima、Yasuo Hirai等：《宫颈癌LA期（新术语）的临床治疗——新FlGOla期宫颈鳞状细胞癌的治疗》第37期子宫癌研究组记录（子宫癌研究组编） 38-43（1999）

H.Yoshikawa, Y.Hirai et al.: "Human papillomavirus infection and other risk factors for cervical intraepithelial neoplasia in Japan" British Journal of Cancer. in press. (1999)

H.Yoshikawa、Y.Hirai 等人：“日本人乳头瘤病毒感染和宫颈上皮内瘤变的其他危险因素”英国癌症杂志。

石谷敬之, 平井康夫、他: "混合癌をふくむ子宮体部明細胞腺癌の臨床細胞学的検討" 日本臨床細胞学会誌. 37(1月5日). (1998)

Noriyuki Ishitani、Yasuo Hirai 等人：“子宫体透明细胞腺癌（包括混合癌）的临床细胞学研究”，日本临床细胞学会杂志 37（1998 年 1 月 5 日）。