Germline deletion and a somatic mutation of the PRKAR1A gene in a Carney complex-related pituitary adenoma

Objective: The objective was to assess involvement of loss of the PRKAR1A gene encoding a type 1α regulatory subunit of cAMP-dependent protein kinase A located on 17q24 in a Carney complex (CNC)-related pituitary adenoma.
Design: We investigated aberrations of the PRKAR1A gene in a CNC patient with a GH-producing pituitary adenoma, whose family has 3 other members with probable CNC.
Methods: A gene mutation was identified by a standard DNA sequencing method based on PCR. DNA copy number was measured to evaluate allelic loss on 17q24 by quantitative PCR. The breakpoints of deletion were determined by cloning a
rearranged region in the deleted allele.
Results: A PRKAR1A mutation of c.751_758del8 (p.S251LfsX16) was found in genomic DNA obtained from a pituitary adenoma, but not leukocytes from the patient.
Reduced DNA copy number at loci including the PRKAR1A gene on 17q24 was detected in both the tumor and leukocytes, suggesting a deletion at the loci at the germline level. The deletion size was determined to be approximately 0.5 Mb and this large deletion was also found in other 2 family members.
Conclusion: This is the first case showing a CNC-related pituitary adenoma with the combination of somatic mutation and a large inherited deletion of the PRKAR1A gene.
Biallelic inactivation of PRKAR1A may be necessary for the development of CNC-related pituitary adenoma.

© 2015 European Society of Endocrinology
Disclaimer: this is not the definitive version of record of this article.This manuscript has been accepted for publication in European Journal of Endocrinology, but the version presented here has not yet been copy-edited, formatted or proofed. Consequently, Bioscientifica accepts no responsibility for any errors or omissions it may contain. The definitive version is now freely available at DOI: 10.1530/EJE-14-0685 2015.