Analysis of gene alterations in the premalignant lesion of colorectum

结直肠癌前病变基因改变分析

• 批准号: 05671063
• 负责人: TOMITA Naohiro
• 金额: $ 1.41万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671063/
• 关键词: p53; K-ras; PCR; microanalysis; adenoma-carcinoma sequence; colon carcinogenesis; carcinoma in adenoma; immunohistochemistry; K‐ras; 大腸癌; 大腸腺腫; adenoma‐carcinoma sequence; 点突然変異; dysplasia; p53遺伝子; 免疫染色

The recent advance in molecular biology revealed that a number of cancer-associated genes play an important role in multistep carcinogenesis in colorectum. However, many of the reports are based on the analysis on a series of colorectal adenoma or carcinoma tissues, and little is known about the timing of the occurence or the precise role of the gene alteration in cach individual case. Carcinoma in adenoma which we used in the present study is the very initial malignancy in adenoma-carcinoma sequence in colon and is thought to be an ideal clinical material for the study of the gene alteration associated with malignant transformation. In addition, microanalysis which we employed enabled us to analyze DNA of both normal cpithelium, adenoma with the different grade of atypia and the carcinoma in each case with the minimal contamination. We are able to compare the result of DNA analysis to the pathological findings including immunohistochemistry, therefore, genetic analysis of histopatholo … More gical level can be done. The result of our present study clearly show that the p53 gene alteration plays a key role in the turning point of malignant conversion from adenoma to carcinoma. Therefore, analysis of p53 gene alteration should be useful also in the clinical application. On the contrary, K-ras gene mutation was shown to be associated with the grade of atypia of adenoma in accordance with the previous reports. There is no difference in the mutation rate of K-ras in between adenoma and carcinoma in adenoma, showing no evidence of the participation of K-ras in malignant transformation. The analysis of K-ras in the multple lesions with the different grade of atypia suggested that K-ras mutaion is merely the consequence of the development of dysplasia. We also did the analysis of genomic instability derived from the abnormality in DNA mismatch repair system and the cell cycle regulator such as WAF1, cyclin D,cdc2/cdk2 in colorectal tumor, and obtained some preliminary results. Some of these result have been already published in the paper as described in this report. Less

分子生物学的最新进展表明，许多肿瘤相关基因在结直肠癌的多步癌变过程中起着重要作用。然而，许多报道是基于对一系列结直肠腺瘤或癌组织的分析，对其发生的时间或基因改变在单个病例中的确切作用知之甚少。腺瘤中的癌是结肠腺瘤-癌序列中最原始的恶性肿瘤，被认为是研究与恶变相关的基因改变的理想临床材料。此外，我们使用的微量分析方法使我们能够以最小的污染分析每个病例的正常上皮、不同级别的非典型性腺瘤和癌的DNA。我们可以将dna分析的结果与包括免疫组织化学在内的病理结果进行比较，因此，对组织病理…的遗传分析。可以做更多的逻辑层面的工作。我们的研究结果清楚地表明，p53基因的改变在腺瘤向癌的恶变转折点中起着关键作用。因此，对P53基因突变的分析在临床上也有一定的应用价值。与以往报道相反，K-ras基因突变与腺瘤的异型性程度有关。K-ras基因突变率在腺瘤和腺瘤癌中无明显差异，未发现K-ras基因参与恶变的证据。K-ras基因突变在不同程度异型的多个病变中的分析表明，K-ras基因突变仅仅是异型增生发展的结果。我们还对大肠肿瘤中DNA错配修复系统和细胞周期调控因子WAF1、Cyclin D、cdc2/cdk2的异常所致的基因组不稳定性进行了分析，得到了一些初步的结果。其中一些成果已经发表在本报告所述的文件中。较少

项目成果

冨田尚裕 他,: "外科におけるPCR(Polymerase Chain Reaction)臨床応用" 外科. 57. 101-111 (1995)

Naohiro Tomita 等人：“PCR（聚合酶链式反应）在外科手术中的临床应用”Surgery 57. 101-111 (1995)。

Ohue, M.et al.: "A frequent alteration of p53 gene in carcinoma in adenoma of colon." Cancer Res.54. 4798-4804 (1994)

Ohue, M.等人：“结肠腺瘤中 p53 基因的频繁改变。”

冨田尚裕 他,: "癌遺伝子と腫瘍マーカー" Tumor Marker Today. 4. 1-3 (1994)

Naohiro Tomita 等人：“癌症基因和肿瘤标志物”《Tumor Marker Today》（今日肿瘤标志物）4. 1-3 (1994)。

冨田尚裕: "外科におけるPCR(Polymerase Chain Reaction)臨床応用" 外科. 57. 101-111 (1995)

Naohiro Tomita：“PCR（聚合酶链式反应）在外科手术中的临床应用” Surg. 57. 101-111 (1995)

Fukuda,K.: "Immunohistochemical study of retinoblastoma gene expression in colorectal carcinomas." Int.J.Oncol.4. 117-121 (1994)

Fukuda,K.：“结直肠癌中视网膜母细胞瘤基因表达的免疫组织化学研究。”