Objective: The role of Krüppel-like transcription factor 4 ( KLF4 ) mutations in IPMNs with concomitant pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study clarified the rate and effect of KLF4 mutations in IPMN with concomitant PDAC.
Materials and methods: DNA was extracted from 65 formalin-fixed and paraffin-embedded samples from 52 patients including 13 IPMNs with concomitant PDAC and 39 IPMNs alone. A comprehensive screening using next-generation sequencing and then targeted sequencing for KLF4 , GNAS , and KRAS mutations were performed.
Results: In next-generation sequencing screening, KRAS mutations were observed in all samples except for one, GNAS mutation in 2 IPMNs with concomitant PDAC, and a KLF4 mutation in 1 IPMN with concomitant PDAC. Targeted sequence detected KLF4 mutations in 11 of the 52 IPMNs. Concomitant PDAC developed only in the nonintestinal, noninvasive, and branch-duct IPMNs, and KLF4 mutations were more frequent in this IPMN type than in the other type. For this IPMN type with KLF4 mutation, PDAC-prediction sensitivity, specificity, and accuracy were 63%, 82%, and 79%, respectively.
Conclusion: For selected IPMNs with nonintestinal, noninvasive, and branch-duct, genetic assessment might be helpful for predicting the possible development of concomitant PDAC, although a prospective validation study using a larger study population is needed.
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