Elucidation of carcinogenic mechanisms in ulcerative colitis

阐明溃疡性结肠炎的致癌机制

• 批准号: 10671160
• 负责人: SHINOZAKI Masaru
• 金额: $ 1.86万
• 依托单位: The Univ. of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671160/
• 关键词: Ulcerative colitis; Dysplasia; Microsatellite instability; APC; K-ras; dysplasia; RER

The status of genetic alterations in ulcerative colitis (UC)-associated neoplasia (UCAN) was investigated focusing on microsatellite instability (MSI) which is shown in a certain fraction of colorectal carcinomas, and adenomatous polyposis coli (APC) gene and K-ras gene, whose mutations occur in the early stage of sporadic colorectal tumorigenesis. Thirty-one UCAN from 15 UC patients who had undergone colorectal resection at our institution were investigated. There were 8 lesions of invasive carcinoma, 15 high-grade dysplasia (HGD) and 8 low-grade dysplasia (LGD). DNA was extracted from each neoplastic lesion and corresponding non-neoplastic tissue by microdissection method. MSI status at 9 microsatellite loci, loss of heterozygosity (LOH) at APC locus, and K-ras codon 12 point mutation were examined. As for MSI, 4/31 (13%) UCAN (carcinoma : 1/8 (13%). HGD : 2/15 (13%). LGD : 1/8 (13%) were MSI-high (3 or more unstable loci) and 12/31 (39%) UCAN (carcinoma : 3/8 (38%), HGD : 6/15 (40%), LGD : 3/8 (38%) were MSI-low (1 or 2 unstable loci). LOH at APC locus was not found in 9 UCAN from 6 informative (heterozygous) cases. K-ras mutation rate of UCAN was 3/31 (9.7%) (carcinoma : 2/8 (25%), HGD : 1/15 (7%) and LGD : 0/8). MSI is relatively common in UCAN and is present at the early stage of tumorigenesis of UCAN, and the involvement of genetic alterations of APC gene and K-ras gene is small. MSI may act as one of the mechanisms for the increased neoplastic risk in UC, and UCAN may develop through other carcinogenic pathway than sporadic carcinomas.

对溃疡性结肠炎（UC）相关肿瘤（UCAN）的基因改变状况进行了研究，重点关注在某些结直肠癌中表现出的微卫星不稳定性（MSI），以及在散发性结直肠肿瘤发生早期发生突变的腺瘤性结肠息肉病（APC）基因和K-ras基因。对来自在我们机构接受结直肠切除术的 15 名 UC 患者的 31 名 UCAN 进行了调查。浸润癌8个，高度不典型增生(HGD)15个，低度不典型增生(LGD)8个。通过显微切割方法从每个肿瘤病变和相应的非肿瘤组织中提取DNA。检查了 9 个微卫星位点的 MSI 状态、APC 位点的杂合性丢失 (LOH) 以及 K-ras 密码子 12 点突变。至于 MSI，4/31 (13%) UCAN（癌：1/8 (13%)。HGD：2/15 (13%)。LGD：1/8 (13%) 为 MSI 高（3 个或更多不稳定位点），12/31 (39%) UCAN（癌：3/8 (38%)，HGD：6/15 （40%），LGD：3/8 (38%) MSI 低（1 或 2 个不稳定位点）。 6 个信息性（杂合）病例中的 9 个 UCAN 中未发现 APC 基因座的 LOH。 UCAN的K-ras突变率为3/31（9.7%）（癌：2/8（25%），HGD：1/15（7%）和LGD：0/8）。 MSI 在 UCAN 中相对常见，存在于 UCAN肿瘤发生的早期阶段，APC基因和K-ras基因的遗传改变参与程度较小。 MSI可能是UC肿瘤风险增加的机制之一，而UCAN可能通过散发性癌以外的其他致癌途径发生。

项目成果

Naoyuki Umetani et al.: "Genetic Alteration in Ulcerative colitis-associated Neoplasia Focusing on APC,K-ras Gene and Microsatellite instability"Jpn. J. Cancer Res.. 90. 1081-1087 (1999)

Naoyuki Umetani 等人：“溃疡性结肠炎相关肿瘤的基因改变聚焦于 APC、K-ras 基因和微卫星不稳定性”Jpn。

Naoyuki Umetani, et al.: "Genetic Alteration in Ulcerative colitis-associated Neoplasia Focusing on APC, K-ras Gene and Microsatellite instability"Jpn. J. Cancer Res.. 90. 1081-1087 (1999)

Naoyuki Umetani 等：“溃疡性结肠炎相关肿瘤的基因改变聚焦于 APC、K-ras 基因和微卫星不稳定性”Jpn。

Naoyuki Umetani et al.: "Genetic Alteration in Ulcerative Calitx-associated Neoplasis Focusing an APC, K-ras gene and Microsatellite Instability"Jpn. J. Cancer Res.. 90. 1081-1087 (1999)

Naoyuki Umetani 等人：“溃疡性 Calitx 相关肿瘤的基因改变聚焦于 APC、K-ras 基因和微卫星不稳定性”Jpn。