PRSS1A16V germline mutation is common in a cohort of intraductal papillary mucinous neoplasms of the pancreas.
Intraductal papillary mucinous neoplasms of the pancreas are heterogenous lesions with variable malignant potential, suggesting underlying biologic diversity. Although inflammation has been implicated in pancreatic carcinogenesis, its contribution to intraductal papillary mucinous neoplasm biology remains poorly understood. We hypothesized that a subset of intraductal papillary mucinous neoplasms may arise in a pancreatitis-associated biologic background.
Whole-exome sequencing was performed in 11 intestinal-type intraductal papillary mucinous neoplasms to explore unrecognized genetic alterations. The PRSS1 germline variant was subsequently validated by Sanger sequencing in 131 patients with intraductal papillary mucinous neoplasm and 50 control patients with pancreatic neuroendocrine neoplasms. Clinical features and imaging findings suggestive of early chronic pancreatitis were compared between variant carriers and noncarriers.
Whole-exome sequencing identified a pancreatitis-related germline mutation of PRSS1A16V as a candidate variant in intraductal papillary mucinous neoplasm. In the validation cohort, 12 of 131 patients with intraductal papillary mucinous neoplasm (9.2%) harbored the PRSS1A16V variant, whereas none of the controls did (P = .018). Clinicopathologic analysis revealed significantly higher frequencies of preoperative clinical symptoms (6/12, 50%; P = .041) and body weight loss (2/12, 16.7%; P = .0078) in the mutation-positive cohort. Imaging features suggestive of early chronic pancreatitis were observed more frequently in the mutation-positive cohort than in the mutation-negative cohort (6/12 [50%] vs 14/119 [11.8%]; P = .0031).
A subset of intraductal papillary mucinous neoplasms is characterized by a pancreatitis-associated biologic background defined by the PRSS1A16V germline variant and imaging features of early chronic pancreatitis. These findings suggest that microinflammatory processes may contribute to intraductal papillary mucinous neoplasm heterogeneity and highlight a potential link between pancreatitis-related genetic susceptibility and pancreatic neoplasia.
Whole-exome sequencing was performed in 11 intestinal-type intraductal papillary mucinous neoplasms to explore unrecognized genetic alterations. The PRSS1 germline variant was subsequently validated by Sanger sequencing in 131 patients with intraductal papillary mucinous neoplasm and 50 control patients with pancreatic neuroendocrine neoplasms. Clinical features and imaging findings suggestive of early chronic pancreatitis were compared between variant carriers and noncarriers.
Whole-exome sequencing identified a pancreatitis-related germline mutation of PRSS1A16V as a candidate variant in intraductal papillary mucinous neoplasm. In the validation cohort, 12 of 131 patients with intraductal papillary mucinous neoplasm (9.2%) harbored the PRSS1A16V variant, whereas none of the controls did (P = .018). Clinicopathologic analysis revealed significantly higher frequencies of preoperative clinical symptoms (6/12, 50%; P = .041) and body weight loss (2/12, 16.7%; P = .0078) in the mutation-positive cohort. Imaging features suggestive of early chronic pancreatitis were observed more frequently in the mutation-positive cohort than in the mutation-negative cohort (6/12 [50%] vs 14/119 [11.8%]; P = .0031).
A subset of intraductal papillary mucinous neoplasms is characterized by a pancreatitis-associated biologic background defined by the PRSS1A16V germline variant and imaging features of early chronic pancreatitis. These findings suggest that microinflammatory processes may contribute to intraductal papillary mucinous neoplasm heterogeneity and highlight a potential link between pancreatitis-related genetic susceptibility and pancreatic neoplasia.
Authors
Yamamoto Yamamoto, Ideno Ideno, Nakafusa Nakafusa, Araki Araki, Miura Miura, Utsunomiya Utsunomiya, Shigematsu Shigematsu, Shimada Shimada, Yamamoto Yamamoto, Fujimoto Fujimoto, Abe Abe, Watanabe Watanabe, Tamura Tamura, Ikenaga Ikenaga, Nakata Nakata, Fujimori Fujimori, Fujita Fujita, Ohuchida Ohuchida, Onishi Onishi, Ogawa Ogawa, Ishigami Ishigami, Aishima Aishima, Oda Oda
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