胰腺上皮內瘤變和胰腺癌中TGF-β/Smads信號通路相關基因的突變分析

Objective: To investigate the alteration of TGF-β/Smads signal pathway correlated gene in pancreatic intraepithelial neoplasia and pancreatic carcinoma. Methods: Tissue microarray, laser capture microdissection, PCR-SSCP analysis and DNA sequencing were used to detect TGF-β/Smads signal pathway correlated gene mutation in pancreatic intraepithelial neoplasia and pancreatic carcinoma. Results: Homozygous loss of Smad4 allele gene exon8 and exon11 was found in 2 of 23 pancreatic carcinomas; mutation of Smad4 exon8, exon11, TβR-Ⅱ exon3 and Smad2 exon1 was found in 2 cases of PanIN-3 lesions and 5 cases of pancreatic carcinomas. The mutation types included missense mutation, nonsense mutaion and polyA loss. The gene alterations were completely consistent to the results of immunohistochemistry examination. Conclusion: Smad4(DPC4) alteration in TGF-β/Smads signal pathway is an important molecular event and plays a crucial role in the development and progression of par creatic carcinoma.