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DOI: 10.1055/s-2005-837651
J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York
Mutational Analysis of PRKAR1A and Gsα in Sporadic Adrenocortical Tumors
Publication History
Received: June 29, 2004
First decision: October 14, 2004
Accepted: November 19, 2004
Publication Date:
30 May 2005 (online)
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Abstract
Little is known about the pathogenesis of adrenocortical tumors. The cAMP-dependent pathway is physiologically activated by ACTH in adrenocortical cells and different components of this cascade may be altered in some functioning adrenocortical tumors. Recently, mutations of the gene encoding the PKA type 1 A regulatory subunit (R1 A), PRKAR1A, associated with loss of heterozygosity (LOH) at PRKAR1A locus, have been demonstrated in primary pigmented nodular adrenocortical disease (PPNAD), either isolated or associated with Carney complex. Moreover, activating mutations of the Gsα gene (the gsp oncogene) have also been found in a small number of adrenocortical cortisol-secreting adenomas. Aim of this study was to investigate the presence of such genetic alterations on a series of 10 ACTH-independent Cushing syndrome due to non-PPNAD adrenocortical adenomas. The coding sequence of PRKAR1A, evaluated by PCR and direct sequencing analysis, revealed the absence of mutations while heterozygosity for at least 1 polymorphism excluded LOH in most tumors. In one single adenoma gsp mutation was detected. In conclusion, we provide additional evidence that the only mutational changes able to activate the cAMP pathway so far identified, i.e. PRKAR1A mutations and gsp oncogene, are a rare event in adrenocortical tumors.
Key words
Adrenocortical tumors - PKAR1A - Gsα
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1 These two authors contributed equally to this work and are considered as first co-authors
Prof. Anna Spada
Istituto di Scienze Endocrine-Pad. Granelli
Ospedale Maggiore IRCCS
Via Francesco Sforza, 35
20122 Milano
Italy
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Fax: + 39 02 50 32 06 05
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