慢性胰腺炎增生性胰管上皮细胞线粒体DNA突变的意义

Investigation on abnormalities of mitochondrial DNA in chronic pancreatitis with hyperplastic pancreatic ductal cell

目的探讨慢性胰腺炎增生性胰管上皮细胞线粒体DNA调控序列D-环突变的意义。方法利用PCR技术扩增46份来自11例慢性胰腺炎不同程度的胰腺导管增生性上皮细胞和其各自正常组织的线粒体DNA全序列。使用核苷同源序列(BLAST)分析病变组织的线粒体DNA。结果 9份标本D-环共有15个突变点,增生性导管上皮细胞D-环至少存在一个以上异常点。异常D-环随病变进展程度呈进行性增加趋势,从单纯性导管上皮细胞肥大性增生的26．1％增至腺瘤样增生的80．0％(P< 0．01)。结论 D-环异常程度与病变程度近乎呈平行性发展,异常D-环可作为检测增生性胰管上皮性组织病变的标志物。

Objectives To investigate the alterations of mitochondrial DNA D-loop in ductal lesions of chronic pancreatitis. Methods The mitochondrial D-loop in 46 ductal lesions of the pancreas including ductal hyperplasia epithelial cells in 11 patients with different degrees of chronic pancreatitis and paired normal tissues from same patients were studied by polymerase chain reaction. Somatic point mutations and sequence variants of D-loop were searched by direct sequencing. DNA samples were sequenced to identify the mutations. Results A total number of 15 alterations existed in D-loops of 9 samples. D-loops in ductal hyperplasia epithelial cells displayed at least one variants. There was a clear increase in incidence of abnormal D-loop from histologically pancreatic duct hypertrophy （26. 1%） to adenomoid hyperplasia （80.0%,P〈 0.01）. Conclusions D-loop alterations exhibit an increasing occurrence that parallels with the histological severity of pre-neoplastic change. These alterations may be the valuable markers for tracking histopathological progression of chronic pancreatitis to pancreatic cancer.