Researchers have identified gene fusions in pancreatic and biliary intraductal oncocytic papillary neoplasms (IOPNs), precursors to pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma, which previously had no recurrent genomic alterations described.

The identification of these gene fusions could have important implications and could aid in classification of cystic lesions in the pancreas.

“Some pancreatic cysts are entirely benign, while others have significant malignant potential,” the researchers wrote. “Fluid can be aspirated from pancreatic cysts and both the DNA and RNA from the cyst fluid can be sequenced. The patterns of genetic alterations identified in the cyst fluid can then be used to classify the cyst type, and guide management.”

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The researchers analyzed 20 resected pancreatic IOPNs and 3 resected biliary IOPNs using broad RNA-based targeted sequencing. All of the samples were found to have recurring fusions of either ATP1B1-PRKACB (13 samples), DNAJB1-PRKACA (6 samples), or ATP1B1-PRKACA (4 samples).

Preoperative specimens from 4 invasive PDACS and 2 intrahepatic cholangiocarcinomas were available from the same patients as the IOPNs, and the researchers found these fusions in the corresponding carcinomas.

Finally, the researchers looked at samples of pancreatic cyst fluid and bile duct brushings, and these fusions were found there as well.

None of the fusions were identified in a group of 126 control pancreatobiliary lesions.

“The unique and ubiquitous nature of PRKACA and PRKACB fusion genes among

pancreatic IOPNs and absence in non-IOPN associated pancreatic lesions supports the recent WHO reclassification of IOPNs as a separate diagnostic entity,” the researchers wrote. “In addition, our study would suggest that IOPNs of the bile duct represent a distinct category of biliary neoplasms and are closely related, by PKA fusion genes, to pancreatic IOPNs.”

Reference

Singhi AD, Wood LD, Parks E, et al. Recurrent rearrangements in PRKACA and PRKACB in intraductal oncocytic papillary neoplasms of the pancreas and bile duct [published online October 30, 2019]. Gastroenterology. doi: 10.1053/j.gastro.2019.10.028