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  • Review Article
  • Published:

Genetic mutations in sporadic pituitary adenomas—what to screen for?

Nature Reviews Endocrinology volume 11, pages 43–54 (2015)Cite this article

Subjects

Key Points

  • More than 95% of pituitary adenomas are sporadic

  • AIP mutations are the most frequent germline mutations found in patients with sporadic isolated pituitary adenomas, and are particularly frequent in children and young adults with macroadenomas or gigantism

  • AIP mutations are almost always inherited from one parent; the penetrance of these mutations requires further evaluation, but seems to be very low

  • The presence of germline MEN1 mutations should be considered a possibility in very young patients with isolated sporadic pituitary adenomas when AIP mutation screening is negative

  • Both AIP and MEN1 are considered to be tumour suppressor genes and might act via regulators of the cell cycle and/or the cAMP pathway

Abstract

Pituitary adenomas are benign intracranial neoplasms that can result in morbidity owing to local invasion and/or excessive or deficient hormone production. The prevalence of symptomatic pituitary adenomas is approximately 1:1,000 in the general population. The vast majority of these tumours occur sporadically and are not part of syndromic disorders. However, germline mutations in genes known to predispose individuals to familial pituitary adenomas are found in a few patients with sporadic pituitary adenomas. Mutations in AIP (encoding aryl-hydrocarbon receptor-interacting protein) are the most frequently observed germline mutations. The prevalence of these mutations in patients with sporadic pituitary adenomas is ∼4%, but can increase to 8–20% in young adults with macroadenomas or gigantism, and also in children. Germline mutations in MEN1 (encoding menin) result in multiple endocrine neoplasia type 1 and are found in very young patients with isolated sporadic pituitary adenomas, which highlights the importance of the chromosome 11q13 locus in pituitary tumorigenesis. In this Review, we describe the clinical features of patients with sporadic pituitary adenomas that are associated with AIP or MEN1 mutations, and discuss the molecular mechanisms that might be involved in pituitary adenoma tumorigenesis. We also discuss genetic screening of patients with sporadic pituitary adenomas and investigations of relatives of these patients who also have the same genetic mutations.

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Figure 1: Characteristics of patients with sporadic pituitary adenomas.
Figure 2: Prevalence of AIP mutations in patients with sporadic pituitary adenomas.
Figure 3: Signalling pathways involved in sporadic pituitary adenomas.

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Acknowledgements

We are grateful to J. Bouligand and J. Young for their continuous support in gene analysis and always very pertinent advice. We also thank L. Cazabat who actively participated in the collection of samples and phenotype–genotype analysis of some of our patients of the Bicêtre Hospital cohort.

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Authors and Affiliations

  1. Service d'Endocrinologie et des Maladies de la Reproduction, AP-HP, Hôpitaux Universitaires Paris-Sud (site Bicêtre), 78 Rue du Général Leclerc, Le Kremlin-Bicêtre, 94270, France

    Anne-Lise Lecoq, Peter Kamenický & Philippe Chanson

  2. Laboratoire de Génétique Moléculaire, Pharmacogénétique et Hormonologie, AP-HP, Hôpitaux Universitaires Paris-Sud (site Bicêtre), 78 Rue du Général Leclerc, Le Kremlin-Bicêtre, 94270, France

    Anne Guiochon-Mantel

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  1. Anne-Lise Lecoq
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Contributions

A.-L.L., P.K. and P.C. researched data for the article, provided substantial contributions to discussion of content and reviewed and edited the manuscript before submission. A.-L.L. wrote the article. A.G.-M. reviewed and edited the manuscript before submission.

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Correspondence to Philippe Chanson.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

AIP mutations and clinical presentation at diagnosis of patients with sporadic pituitary adenomas (DOC 131 kb)

Supplementary Table 2

MEN1 mutations and clinical characteristics of patients with sporadic pituitary adenomas (DOC 46 kb)

Supplementary Table 3

Germline mutations, somatic mutation and epigenetic modifications associated with 'apparently' sporadic pituitary adenomas (DOC 127 kb)

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Lecoq, AL., Kamenický, P., Guiochon-Mantel, A. et al. Genetic mutations in sporadic pituitary adenomas—what to screen for?. Nat Rev Endocrinol 11, 43–54 (2015). https://doi.org/10.1038/nrendo.2014.181

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