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Gs alpha and Gi2 alpha mutations in clinically non-functioning pituitary tumours
E A Williamson1, M Daniels, S Foster
1Department of Medicine, Medical School, Newcastle upon Tyne, UK.
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.
Insights
Activating G protein gene mutations were found in 13% of non-functioning pituitary tumors. These mutations, including dual Gs alpha (gsp) and Gi2 alpha (gip) mutations, were associated with local bone infiltration.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Activating mutations in Gs alpha (gsp) and Gi2 alpha (gip) are implicated in endocrine tumors.
- Non-functioning pituitary tumors (NFTs) are a significant clinical challenge.
Purpose of the Study:
- To determine the prevalence of gsp and gip mutations in NFTs.
- To compare clinical characteristics of pituitary tumors with and without G protein gene mutations.
Main Methods:
- Screened 22 NFTs and 20 normal pituitary glands for G protein gene mutations.
- Utilized site-directed hybridization and direct sequencing of amplified Gs alpha and Gi2 alpha DNA.
Main Results:
- G protein gene mutations were identified in 13% (3/22) of NFTs.
- Two NFTs had gsp mutations, and three had gip mutations; two NFTs had both.
- All tumors with G protein gene mutations showed local bone infiltration.
Conclusions:
- G protein gene mutations are present in a subset of non-functioning pituitary tumors.
- The co-occurrence of gsp and gip mutations suggests a potential stepwise pathogenesis in pituitary neoplasia.