摘要
目的探讨合并慢性胰腺炎的胰腺癌癌旁增生性胰管上皮细胞线粒体DNA调控序列(D-loop)突变的意义。方法利用PCR技术,扩增胰腺导管增生性细胞、癌细胞及其各自正常的胃黏膜上皮细胞的线粒体DNA D-loop。核苷酸序列同源性对比分析,观察病变细胞的D-loop突变频率。结果癌细胞和增生性病变细胞至少存在一个以上的突变点,总突变点为31。突变类型：线粒体DNA 11/12为同质性突变,1/12为异质性突变。D-loop突变频率随病变进展程度呈进行性增加的趋势,异常D-loop由PanIN1的33．3%增加到PanIN3的75．0%(P＜0．01)。结论胰腺导管上皮细胞病变存在着异常D-loop,D-loop异常程度与病变发展程度呈平行性发展。异常D-loop可作为检测胰腺导管上皮性细胞病变的标志物。
Objective. To explore the significance of mitochondrial D-loop alterations in hyperplastic pancreatic ductal cells in vicinity of pancreatic cancer coexisting with chronic pancreatitis. Methods Malignant lesions and foci of pancreatic ductal intraepithelial neoplasia of the pancreas and paired normal gastric mucosal epithelial cells from the same patients, respectively, were assessed by polymerase chain reaction. Somatic point mutations and sequence variants of D-loop were searched by direct sequencing of the mitochondrial genome. D-loops were sequenced by BLAST to identify their mutations. Results Eleven of 12 pancreatic cancers displayed at least one D-loop variants and one tumor presented heteroplasmy. There was an apparent increase in incidence of D-loop mutational rate from PanIN1 （33.3%） to PanIN3 （75%, P 〈 0.01 ）. Conclusion Mitochondrial D-loop alterations in the pancreas occur in the earliest premalignant lesions and exhibite an increasing occurence that parallels histological severity. These alterations may serve as a valuable marker to follow the histopathological progression of the lesions. Large number of further studies are required to clarify clinical implications of the mitochondrial DNA alterations.
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2006年第6期433-437,共5页
Chinese Journal of Oncology
关键词
胰腺炎
胰腺癌
癌旁增生性胰管上皮细胞
Pancreatitis
Pancreatic cancer
Hyperplastic pancreatic ductal cells
