title: Pancreatic ductal and acinar cell neoplasms in Carney complex: a possible new association.
abstract: BACKGROUND
  Carney complex (CNC) is a rare disease inherited as an autosomal dominant trait, associated with various tumors, and caused most frequently by inactivation of the PRKAR1A gene.
  
  
  OBJECTIVE
  In our recent investigation of a large cohort of CNC patients, we identified several cases of pancreatic neoplasms. This possible association and PRKAR1A's possible involvement in pancreatic tumor have not been reported previously.
  
  
  METHODS
  Nine patients (2.5%) with CNC and pancreatic neoplasms in an international cohort of 354 CNC patients were identified; we studied six of them. Immunohistochemistry and PRKAR1A sequencing were obtained.
  
  
  RESULTS
  Three men and three women with a mean age of 49 yr (range 34-75 yr) had acinar cell carcinoma (n = 2), adenocarcinoma (n = 1), and intraductal pancreatic mucinous neoplasm (n = 3). Five patients had a germline PRKAR1A mutation, including two patients with acinar cell carcinoma, for whom mutations were found in a hemizygous state in the tumor, suggesting loss of heterozygosity. PRKAR1A expression was not detected in five of the six pancreatic neoplasms from CNC patients, whereas the protein was amply expressed on other sporadic pancreatic tumors and normal tissue.
  
  
  CONCLUSIONS
  An unexpectedly high prevalence of rare pancreatic tumors was found among CNC patients. Immunohistochemistry and loss-of-heterozygosity studies suggest that PRKAR1A could function as a tumor suppressor gene in pancreatic tissue, at least in the context of CNC. Clinicians taking care of CNC patients should be aware of the possible association of CNC with a potentially aggressive pancreatic neoplasm.
authors: Institut National de la Santé et de la Recherche Médicale–Unité 1016, France.
authors: Sébastien
authors: S
authors: Gaujoux
authors: Frédérique
authors: F
authors: Tissier
authors: Bruno
authors: B
authors: Ragazzon
authors: Vinciane
authors: V
authors: Rebours
authors: Emmanouil
authors: E
authors: Saloustros
authors: Karine
authors: K
authors: Perlemoine
authors: Caroline
authors: C
authors: Vincent-Dejean
authors: Guillaume
authors: G
authors: Meurette
authors: Elisabeth
authors: E
authors: Cassagnau
authors: Bertrand
authors: B
authors: Dousset
authors: Xavier
authors: X
authors: Bertagna
authors: Anelia
authors: A
authors: Horvath
authors: Benoit
authors: B
authors: Terris
authors: J Aidan
authors: JA
authors: Carney
authors: Constantine A
authors: CA
authors: Stratakis
authors: Jérôme
authors: J
authors: Bertherat
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D018267:Carcinoma, Acinar Cell / Q000235:genetics* / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D056733:Carney Complex / Q000235:genetics* / Q000473:pathology; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; C517834:PRKAR1A protein, human