Significance of the mitochondrial D-loop alterations in hyperplastic pancreatic ductal cells in the vicinity of pancreatic cancer coexisting with chronic pancreatitis / 中华肿瘤杂志

ABSTRACT

<p><b>OBJECTIVE</b>To explore the significance of mitochondrial D-loop alterations in hyperplastic pancreatic ductal cells in vicinity of pancreatic cancer coexisting with chronic pancreatitis.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>