RER+结直肠癌组织转化生长因子βⅡ型受体的突变  

Transforming growth factor β receptor Ⅱ mutations in RER positive colorectal cancers

作　　者：来茂德[1] 黄智达[1] 黄琼[1] 陈俭[1] 

机构地区：[1]浙江大学医学院病理学教研室,杭州310031

出　　处：《中华病理学杂志》2004年第1期6-10,共5页Chinese Journal of Pathology

基　　金：国家自然科学基金资助项目(39770 2 97)

摘　　要：目的　检测转化生长因子 βⅡ型受体 (TGF βRⅡ ) (A) 10 、TGF βRⅡ (GT) 3、TGF βRⅡ 452 /454、TGF βRⅡ 53 3、hMSH3 (A) 8、hMSH6(C) 8、Bax (G) 8、胰岛素样生长因子Ⅱ型受体 (IGFⅡR) (G) 8、IGFⅡR (CT) 3 等微卫星突变热点及TGF βRⅡ点突变在RER +结直肠癌中的突变率、突变发生在肿瘤进程的哪一阶段。方法　采用聚合酶链反应 单链长度多态性分析 (PCR SSLP)、微切割 PCR SSLP、PCR 单链构象多态性分析、克隆测序、免疫组织化学对 76例结直肠癌标本进行分析。结果　RER +(replicationerrorpositive)肿瘤TGF βRⅡ (A) 10 突变率约为 3 / 9,突变可发生于重度不典型增生腺瘤。其余位点未见突变。RER +结直肠癌多见于男性 ,发病年龄较早 (P <0 0 5) ;肿瘤多位于结肠 (P <0 0 5)。结论　RER +结直肠癌多见于较年轻男性 ,好发于结肠 ,仅约三分之一病例存在TGF βRⅡ(A) 10 突变 ;TGF βRⅡ (A) 10 突变发生于重度不典型增生腺瘤 ,可能对RER +腺瘤进展为癌起重要作用。RER +结直肠癌在临床病例特征上与西方发达国家的病例存在差异 。ObjectiveTo detect alteratio ns of microsatellite loci [transforming growth factor β receptor Ⅱ (TGF-βRⅡ )(A) 10 、 TGF-βRⅡ (GT) 3、hMSH3 (A) 8、hMSH6 (C) 8、Bax (G) 8、IGFⅡR (G) 8、IGFⅡR (CT) 3] and point mutations of TGF-βRⅡ(TGF-βRⅡ 452/454、TGF-βRⅡ 533). MethodsPCR-SSLP, microdissection-PCR-SSLP,PCR-SSCP,clone sequencing and immunohistochemistry were used. ResultsThe mutation rate of TGF-βRⅡ(A) 10 in RER+(replication error positive) colorectal carcinomas was 33%(3/9). Similar mutations were also observed in adenomas with severe dysplasia. No mutations at other microsatellite loci were found. RER+ colorectal cancers mainly occurred in male patients at a young age and were more common in the colon than in the rectum (P< 0.05). Con clusionsRER+ colorectal cancers were found in young males and commonly located in the colon. A one third mutation rate in TGF-βRⅡ(A) 10 in these patients is lower than that observed in western populations, which may imply diverse pathways of carcinogenesis of RER+ colorectal carcinoma. TGF-βRⅡ(A) 10 mutation may play a role in the transforming process from an adenoma with severe dysplasia to a full blown carcinoma.

关 键 词：RER 结直肠癌 组织转化生长因子βⅡ型受体 基因突变 检测 发病机制 

分 类 号：R735.3[医药卫生—肿瘤]