Sequence analysis of the catalytic subunit of PKA in somatotroph adenomas.

Abstract

OBJECTIVE:

The pathogenetic mechanisms of sporadic somatotroph adenomas are not well understood, but derangements of the cAMP pathway have been implicated. Recent studies have identified L206R mutations in the alpha catalytic subunit of protein kinase A (PRKACA) in cortisol-producing adrenocortical adenomas and amplification of the beta catalytic subunit of protein kinase A PRKACB in acromegaly associated with Carney complex. Given that both adrenocortical adenomas and somatotroph adenomas are known to be reliant on the cAMP signalling pathway, we sought to determine the relevance of the L206R mutation in both PRKACA and PRKACB for the pathogenesis of sporadic somatotroph adenomas.

DESIGN:

Somatotroph adenoma specimens, both frozen and formalin-fixed, from patients who underwent surgery for their acromegaly between 1995 and 2012, were used in the study.

METHODS:

The DNA sequence at codon 206 of PRKACA and PRKACB was determined by PCR amplification and sequencing. The results were compared with patient characteristics, the mutational status of the GNAS complex locus and the tumour granulation pattern.

RESULTS:

No mutations at codon 206 of PRKACA or PRKACB were found in a total of 92 specimens, comprising both WT and mutant GNAS cases, and densely, sparsely and mixed granulation patterns.

CONCLUSIONS:

It is unlikely that mutation at this locus is involved in the pathogenesis of sporadic somatotroph adenoma; however, gene amplification or mutations at other loci or in other components of the cAMP signalling pathway, while unlikely, cannot be ruled out.

• Authors: Sarah J Larkin, Francesco Ferraù, Niki Karavitaki, Laura C Hernández-Ramírez, Olaf Ansorge, Ashley B Grossman, Márta Korbonits
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 171 Issue 6 Pg. 705-10 (Dec 2014) ISSN: 1479-683X [Electronic] England
• PMID: 25225481 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 European Society of Endocrinology.

Chemical References

• Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
• PRKACA protein, human

Topics

• Adenoma (genetics, pathology)
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Child
• Cyclic AMP-Dependent Protein Kinase Catalytic Subunits (genetics)
• Female
• Growth Hormone-Secreting Pituitary Adenoma (genetics, pathology)
• Humans
• Male
• Middle Aged
• Mutation
• Sequence Analysis, DNA
• Tumor Burden (genetics)
• Young Adult