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http://purl.uniprot.org/citations/37871652http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/37871652http://www.w3.org/2000/01/rdf-schema#comment"Intraductal oncocytic papillary neoplasms (IOPNs) are distinct from intraductal papillary mucinous neoplasms based on characteristic morphologic and genetic features represented by fusion genes involving PRKACA or PRKACB (PRKACA/B). However, pancreatic and biliary tumors with partial oncocytic features are often encountered clinically, and their molecular features are yet to be clarified. This study included 80 intraductal papillary neoplasms: 32 tumors with mature IOPN morphology (typical), 28 with partial or subclonal oncocytic features (atypical), and 20 without oncocytic features (control). We analyzed PRKACA/B fusion genes, including ATP1B1::PRKACA, DNAJB1::PRKACA, and ATP1B1::PRKACB, by reverse-transcription PCR; mRNA expression of fusion genes and nonrearranged PRKACA/B genes by quantitative reverse-transcription PCR; mutations in KRAS, BRAF, and GNAS by targeted sequencing or droplet digital PCR; and the expression of cyclic adenosine monophosphate (cAMP)-dependent protein kinase catalytic subunits α (PRKACA) and β (PRKACB), phosphorylated cAMP response element-binding protein, and aberrations of p16, p53, SMAD4, STK11, and β-catenin by immunohistochemistry. PRKACA/B fusion genes were detected in 100% (32/32) of typical, 46% (13/28) of atypical, and 0% (0/20) of control (P < .05). Expression of PRKACA, PRKACB, and phosphorylated cAMP response element-binding protein was upregulated in neoplasms with PRKACA/B fusion genes (P < .05). mRNA expression of the PRKACA/B fusion genes and protein expression of PRKACA or PRKACB tended to be higher in typical than in atypical cases (mRNA, P = .002; protein expression, P = .054). In some atypical neoplasms with mixed subtypes, PRKACA/B fusion genes were superimposed exclusively on oncocytic components. Typical IOPNs harbored fewer KRAS and GNAS mutations than control samples and fewer alterations in p53 and STK11 than atypical samples (P < .05). In conclusion, PRKACA/B fusion genes not only are the characteristic drivers of IOPNs but also play a crucial role in the development of subclonal oncocytic neoplasms. Moreover, oncocytic morphology is strongly associated with upregulation of PRKACA/B, which may provide clues for potential therapeutic options."xsd:string
http://purl.uniprot.org/citations/37871652http://purl.org/dc/terms/identifier"doi:10.1016/j.modpat.2023.100358"xsd:string
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/author"Itoh T."xsd:string
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/author"Aoki S."xsd:string
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/author"Okamura Y."xsd:string
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/author"Ishida M."xsd:string
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/author"Mizukami Y."xsd:string
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/author"Ono Y."xsd:string
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/author"Kinoshita K."xsd:string
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/author"Unno M."xsd:string
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/author"Hirose K."xsd:string
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/author"Furukawa T."xsd:string
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/author"Omori Y."xsd:string
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/author"Higuchi R."xsd:string
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/author"Morikawa T."xsd:string
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/author"Honda G."xsd:string
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/author"Seino M."xsd:string
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/author"Date F."xsd:string
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/author"Mizuma M."xsd:string
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/date"2024"xsd:gYear
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/name"Mod Pathol"xsd:string
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/pages"100358"xsd:string
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/title"Gene Rearrangement and Expression of PRKACA and PRKACB Govern Morphobiology of Pancreatobiliary Oncocytic Neoplasms."xsd:string
http://purl.uniprot.org/citations/37871652http://purl.uniprot.org/core/volume"37"xsd:string
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