High-Throughput Mutation Profiling in Intraductal Papillary Mucinous Neoplasm (IPMN)

Background: Specific mutations leading to the development of various histological grades of intraductal papillary mucinous neoplasm (IPMN) have been partially characterized. Methods: Analysis of 323 oncogenic mutations in 22 tumor-related genes was conducted, using a chip-based matrix-assisted laser desorption time-of-flight mass spectrometer of DNA extracted from microdissected cells of low-grade (n = 14), borderline (n = 6), and invasive IPMN (n = 7). Additional assays were performed on the DNA extracted from dyplastic cells found in the background of the adenocarcinoma. Results: We identified 9 K-ras mutations (low grade, 2/14; borderline, 1/6; invasive, 6/7), 3 p53 mutations (low grade, 1/14; invasive 2/7), and 2 PIK3CA mutations (low grade, 1/14; invasive, 1/7). K-ras, p53, and PIK3CA mutations present in the invasive cancer were absent in the adjacent precursor cells in 50% of the cases. In one patient, K-ras mutation was present in the precursor lesion and absent in the adjacent invasive lesion. Conclusions: Of the 22 screened tumor-related genes, only K-ras, p53, and PIK3CA mutations were found in IPMN. K-ras mutations are more prevalent in invasive than premalignant IPMN. The variable coexistence of mutations in the invasive cancer and in the adjacent precursor cells may point to the heterogeneous nature of this tumor.