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Analysis of genetic variants of phosphodiesterase 11A in acromegalic patients

E Peverelli1, F Ermetici, M Filopanti

  • 1Endocrinology and Diabetology Unit, Department of Medical Sciences, University of Milan, Padiglione Granelli, Fondazione Ospedale Maggiore IRCCS, Via F Sforza, 35, 20122 Milan, Italy.

European Journal of Endocrinology
|August 13, 2009
PubMed
Abstract

Insights

Phosphodiesterase type 11A (PDE11A) gene variants were found in acromegalic patients, slightly more often than in controls. These PDE11A variants may only marginally contribute to somatotropinoma development.

Area of Science:

  • Endocrinology
  • Molecular Genetics
  • Oncology

Background:

  • Aberrant cyclic adenosine monophosphate (cAMP) signaling is implicated in the pathogenesis of somatotropinomas.
  • Phosphodiesterase type 11A (PDE11A) gene variants have been recently identified in adrenocortical and testicular tumors.

Purpose of the Study:

  • To screen acromegalic patients for the presence of PDE11A gene variants.
  • To investigate the role of PDE11A variants in the development of somatotropinomas.

Main Methods:

  • Sequencing of the PDE11A gene-coding region in 78 acromegalic patients and 110 controls.
  • Immunohistochemistry for PDE11A expression in somatotropinomas and normal pituitary samples.

Main Results:

  • Fifteen nonsynonymous germline substitutions in PDE11A were identified in 13 acromegalic patients (17%), a prevalence only slightly higher than in controls (14%).
  • PDE11A expression was higher in somatotropinomas than normal pituitary tissue, with reduced staining in tumors harboring specific variants or loss of heterozygosity.
  • No significant clinical or hormonal differences were observed, though PDE11A variant carriers showed a trend towards more aggressive tumors.

Conclusions:

  • This study demonstrates the presence of PDE11A variants in a subset of acromegalic patients.
  • The findings suggest that PDE11A variants may play a marginal role in somatotropinoma development due to normal enzyme expression in most tumors and lack of significant clinical phenotype.

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