Methylation of mismatch repair gene and E-cadherin gene abnormality in serrated adenoma of the colorectum

结直肠锯齿状腺瘤错配修复基因甲基化及E-cadherin基因异常

基本信息

批准号：
13670167
负责人：
AJIOKA Yoichi
金额：
$ 2.18万
依托单位：
NIIGATA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670167/
关键词：
colorectal adenoma serrated adenoma APC E-cadherin hMLH1 methylation gene alteration mucus phenotype MSI hMLH1

项目摘要

APC, E-cadherin gene mutation and methylation and hMLH1 gene methylation, and mucus phenotype of colorectal serrated adenoma (SA) were investigated and compared with those of tubular adenoma (TA).1. APC : Both mutation (exon 1 to 7) and methylation rate of SA [3% (1/34), 19.2% (5/23)] were significantly lower that those of TA [40% (4/10), 90% (9/10)] (p<0.005).2. E-cadherin : No significant difference was found in mutation (exon 6-9) and methylation rate between SA [6% (2/34), 68% (23/24)] and TA [0% (0/10), 50% (5/10)]. Mutation found in SA was identical with that found in gastric carcinoma with gastric mucus phenotype (18-base pair deletion of codon 418 to 423).3. hMLH1: methylation was found in 88% (30/34) of SA.4. Mucus phenotype: Although there was no significant difference in MUC5AC expression between SA[93.5% (29/31)] and TA[90.5% (19/21)], MUC6 was highly expressed in SA[71% (22/31)] than TA[14.3% (3/21)] (p<0.0001).5. Conclusion and Discussion : APC and E-cadherin alterations would not play a role in the development of SA. Role of abnormality in hMLH1 remained to be elucidated. Expression of MUC6 (gastric pyloric type core protein) was the characteristic phenotype of SA. Identical mutational pattern seen in SA and gastric carcinoma with gastric phenotype suggested a possibility that neoplasia with gastric mucus phenotype, regardless of organ, may be involved in common genetic alterations.

检测结直肠锯齿状腺瘤(SA)的APC、E-cadherin基因突变和甲基化、hMLH1基因甲基化、粘液表型，并与管状腺瘤(TA)进行比较。 1． APC ： SA 的突变（外显子 1 至 7）和甲基化率 [3% (1/34)、19.2% (5/23)] 均显着低于 TA [40% (4/10)、90%] (9/10)] (p<0.005).2。 E-钙粘蛋白：SA[6%(2/34)、68%(23/24)]和TA[0%(0/10)、 50% (5/10)]。 SA中发现的突变与具有胃粘液表型的胃癌中发现的突变相同(密码子418至423的18碱基对缺失)。3． hMLH1：在 88% (30/34) 的 SA.4 中发现甲基化。粘液表型：虽然SA[93.5%(29/31)]和TA[90.5%(19/21)]之间MUC5AC表达无显着差异，但MUC6在SA[71%(22/31)]中高表达比 TA[14.3% (3/21)] (p<0.0001).5。结论与讨论：APC 和 E-cadherin 的改变不会在 SA 的发生中发挥作用。 hMLH1 异常的作用仍有待阐明。 MUC6（胃幽门型核心蛋白）的表达是SA的特征表型。在 SA 和具有胃表型的胃癌中观察到的相同突变模式表明，具有胃粘液表型的肿瘤，无论器官如何，都可能涉及常见的遗传改变。