Key result
Carney complex was associated with an unexpectedly high prevalence (2.5%) of rare pancreatic tumors, with PRKAR1A loss of heterozygosity suggesting a tumor suppressor role in this context.
Cohort (n=354)
Yes
Carney complex is associated with an unexpectedly high prevalence of potentially aggressive pancreatic neoplasms, likely driven by PRKAR1A inactivation.
May support pancreatic surveillance in Carney complex; leaves open PRKAR1A tumor suppressor role pending prospective studies.
CONTEXT: 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. OBJECTIVES: 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. PATIENTS AND 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. CONCLUSION: 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.
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Gaujoux et al. (2011) conducted a cohort in Carney complex and pancreatic neoplasms (n=354). Carney complex (PRKAR1A mutation) vs. Sporadic pancreatic tumors and normal tissue was evaluated on Prevalence of pancreatic neoplasms. Carney complex was associated with an unexpectedly high prevalence (2.5%) of rare pancreatic tumors, with PRKAR1A loss of heterozygosity suggesting a tumor suppressor role in this context.
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