Year: 2011
Type: article
Abstract: 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.
DOI: 10.1210/jc.2011-1433
Authors: Sébastien Gaujoux, Frédérique Tissier, Bruno Ragazzon, Vinciane Rebours, Emmanouil Saloustros, Karine Perlemoine, Caroline Vincent-Dejean, Guillaume Meurette, Elisabeth Cassagnau, Bertrand Dousset, Xavier Bertagna, Anelia Horvath, Benoit Terris, J. Aidan Carney, Constantine A. Stratakis, Jérôme Bertherat
Institutions: Centre National de la Recherche Scientifique, Inserm, Hôpital Cochin, Assistance Publique – Hôpitaux de Paris, Institut Cochin, Institut National du Cancer, Université Paris Descartes, Hôpital Beaujon, National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Centre Hospitalier Universitaire de Nantes, Mayo Clinic
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1968621017