GS-ALPHA AND GI2-ALPHA MUTATIONS IN CLINICALLY NONFUNCTIONING PITUITARY-TUMORS

BACKGROUND AND OBJECTIVE Activating mutations of Gsa (gsp) and Gi2 alp ha: (gip) have been described in various endocrine neoplastic conditio ns. The objective of this study was to assess the prevalence of gsp an d gip mutations in clinically non-functioning pituitary tumours (NFTs) and to compare the clinical phenotypic characteristics of tumours bea ring G protein gene mutations with wild-type tumours. DESIGN Twenty-tw o 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 poly merase chain reaction amplified Gsa and Gi2 alpha DNA. RESULTS G prote in gene mutations were identified in 3/22 (13%) of NFTs. Two tumours d emonstrated gsp mutations, one at codon 201 arginine to cysteine, and the second at codon 227 glutamine to arginine. Three tumours demonstra ted gip mutations at codon 205 glutamine to arginine. Two tumours with gsp mutations also harboured gip mutations. Al tumours with G protein gene mutations demonstrated local bone infiltration into the surround ing structures. CONCLUSIONS G protein gene mutations have been demonst rated in a proportion of non-functioning pituitary tumours. The presen ce of dual gsp and gip mutations in two tumours suggests the possibili ty of multiple hits in a stepwise pathogenesis of pituitary neoplasia.