Recurrent Rearrangements in PRKACA and PRKACB in Intraductal Oncocytic Papillary Neoplasms of the Pancreas and Bile Duct.
Adult
Aged
Bile Duct Neoplasms
/ genetics
Bile Ducts, Intrahepatic
Carcinoma, Pancreatic Ductal
/ genetics
Cholangiocarcinoma
/ genetics
Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
/ genetics
Female
Gene Fusion
Gene Rearrangement
HSP40 Heat-Shock Proteins
/ genetics
Humans
Male
Middle Aged
Pancreatic Cyst
/ genetics
Pancreatic Intraductal Neoplasms
/ genetics
Pancreatic Neoplasms
/ genetics
Sodium-Potassium-Exchanging ATPase
/ genetics
CCA
Diagnostic Factor
Kinase A
Liver
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
17
06
2019
revised:
22
10
2019
accepted:
25
10
2019
pubmed:
5
11
2019
medline:
9
4
2020
entrez:
4
11
2019
Statut:
ppublish
Résumé
Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreas and bile duct contain epithelial cells with numerous, large mitochondria and are cystic precursors to pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA), respectively. However, IOPNs do not have the genomic alterations found in other pancreatobiliary neoplasms. In fact, no recurrent genomic alterations have been described in IOPNs. PDACs without activating mutations in KRAS contain gene rearrangements, so we investigated whether IOPNs have recurrent fusions in genes. We analyzed 20 resected pancreatic IOPNs and 3 resected biliary IOPNs using a broad RNA-based targeted sequencing panel to detect cancer-related fusion genes. Four invasive PDACs and 2 intrahepatic CCAs from the same patients as the IOPNs, were also available for analysis. Samples of pancreatic cyst fluid (n = 5, collected before surgery) and bile duct brushings (n = 2) were analyzed for translocations. For comparison, we analyzed pancreatobiliary lesions from 126 patients without IOPN (controls). All IOPNs evaluated were found to have recurring fusions of ATP1B1-PRKACB (n = 13), DNAJB1-PRKACA (n = 6), or ATP1B1-PRKACA (n = 4). These fusions also were found in corresponding invasive PDACs and intrahepatic CCAs, as well as in matched pancreatic cyst fluid and bile duct brushings. These gene rearrangements were absent from all 126 control pancreatobiliary lesions. We identified fusions in PRKACA and PRKACB genes in pancreatic and biliary IOPNs, as well as in PDACs and pancreatic cyst fluid and bile duct cells from the same patients. We did not identify these gene fusions in 126 control pancreatobiliary lesions. These fusions might be used to identify patients at risk for IOPNs and their associated invasive carcinomas.
Sections du résumé
BACKGROUND & AIMS
Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreas and bile duct contain epithelial cells with numerous, large mitochondria and are cystic precursors to pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA), respectively. However, IOPNs do not have the genomic alterations found in other pancreatobiliary neoplasms. In fact, no recurrent genomic alterations have been described in IOPNs. PDACs without activating mutations in KRAS contain gene rearrangements, so we investigated whether IOPNs have recurrent fusions in genes.
METHODS
We analyzed 20 resected pancreatic IOPNs and 3 resected biliary IOPNs using a broad RNA-based targeted sequencing panel to detect cancer-related fusion genes. Four invasive PDACs and 2 intrahepatic CCAs from the same patients as the IOPNs, were also available for analysis. Samples of pancreatic cyst fluid (n = 5, collected before surgery) and bile duct brushings (n = 2) were analyzed for translocations. For comparison, we analyzed pancreatobiliary lesions from 126 patients without IOPN (controls).
RESULTS
All IOPNs evaluated were found to have recurring fusions of ATP1B1-PRKACB (n = 13), DNAJB1-PRKACA (n = 6), or ATP1B1-PRKACA (n = 4). These fusions also were found in corresponding invasive PDACs and intrahepatic CCAs, as well as in matched pancreatic cyst fluid and bile duct brushings. These gene rearrangements were absent from all 126 control pancreatobiliary lesions.
CONCLUSIONS
We identified fusions in PRKACA and PRKACB genes in pancreatic and biliary IOPNs, as well as in PDACs and pancreatic cyst fluid and bile duct cells from the same patients. We did not identify these gene fusions in 126 control pancreatobiliary lesions. These fusions might be used to identify patients at risk for IOPNs and their associated invasive carcinomas.
Identifiants
pubmed: 31678302
pii: S0016-5085(19)41481-9
doi: 10.1053/j.gastro.2019.10.028
pmc: PMC7010554
mid: NIHMS1543106
pii:
doi:
Substances chimiques
ATP1B1 protein, human
0
DNAJB1 protein, human
0
HSP40 Heat-Shock Proteins
0
Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
EC 2.7.11.11
PRKACA protein, human
EC 2.7.11.11
PRKACB protein, human
EC 2.7.11.11
Sodium-Potassium-Exchanging ATPase
EC 7.2.2.13
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
573-582.e2Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK120531
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA062924
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA200466
Pays : United States
Informations de copyright
Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.
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