LAUSR

We aimed to assess some of the potential genetic pathways for cancer development from non-malignant intraductal papillary mucinous neoplasm (IPMN) by evaluating genetic mutations and methylation. In total, 46 dissected regions in 33 IPMN cases were analyzed and compared between malignant-potential and benign cases, or between malignant-potential and benign tissue dissected regions including low-grade IPMN dissected regions accompanied by malignant-potential regions. Several gene mutations, gene methylations, and proteins were assessed by pyrosequencing and immunohistochemical analysis. RASSF1A methylation was more frequent in malignant-potential dissected regions ( p  = 0.0329). LINE-1 methylation was inversely correlated with GNAS mutation ( r  =  − 0.3739, p  = 0.0105). In cases with malignant-potential dissected regions, GNAS mutation was associated with less frequent perivascular invasion ( p  = 0.0128), perineural invasion ( p  = 0.0377), and lymph node metastasis ( p  = 0.0377) but significantly longer overall survival, compared to malignant-potential cases without GNAS mutation ( p  = 0.0419). The presence of concordant KRAS and GNAS mutations in the malignant-potential and benign dissected regions were more frequent among branch-duct IPMN cases than among the other types ( p  = 0.0319). Methylation of RASSF1A , CDKN2A , and LINE-1 and GNAS mutation may be relevant to cancer development, IPMN subtypes, and cancer prognosis.