Gs alpha and Gi2 alpha mutations in clinically non-functioning pituitary tumours

Abstract

Background and objective: Activating mutations of Gs alpha (gsp) and Gi2 alpha (gip) have been described in various endocrine neoplastic conditions. The objective of this study was to assess the prevalence of gsp and gip mutations in clinically non-functioning pituitary tumours (NFTs) and to compare the clinical phenotypic characteristics of tumours bearing G protein gene mutations with wild-type tumours.

Design: Twenty-two NFTs and 20 normal anterior pituitary glands screened for G protein gene mutations.

Patients: Twenty-two patients; 14 female (median age 59 years, range 19-76) and 8 males (median age 66.5 years, range 50-77).

Measurements: Site-directed hybridization or direct sequencing of polymerase chain reaction amplified Gs alpha and Gi2 alpha DNA.

Results: G protein gene mutations were identified in 3/22 (13%) of NFTs. Two tumours demonstrated gsp mutations, one at codon 201 arginine to cysteine, and the second at codon 227 glutamine to arginine. Three tumours demonstrated gip mutations at codon 205 glutamine to arginine. Two tumours with gsp mutations also harboured gip mutations. All tumours with G protein gene mutations demonstrated local bone infiltration into the surrounding structures.

Conclusions: G protein gene mutations have been demonstrated in a proportion of non-functioning pituitary tumours. The presence of dual gsp and gip mutations in two tumours suggests the possibility of multiple hits in a stepwise pathogenesis of pituitary neoplasia.