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Genetic and functional aberrations of guanine nucleotide-binding protein, alpha stimulating ( GNAS ), aryl hydrocarbon receptor interacting protein ( AIP ), and pituitary tumor transforming gene ( PTTG ) are among the most prominent events in pituitary tumorigenesis. A cohort of Brazilian patients with somatotropinomas (n=41) and non-functioning pituitary adenomas (NFPA, n=21) from a single tertiary-referral center were evaluated for  GNAS  and  AIP  mutations and gene expression of  AIP  and  PTTG . Results were compared to the clinical and biological (Ki67 and p53 expression) characteristics of tumors and their response to therapy, if applicable. Genetic analysis revealed that 27% of somatotropinomas and 4.8% of NFPA harbored  GNAS  mutations (P=0.05). However, no differences were observed in clinical characteristics, tumor extension, response to somatostatin analog therapy, hormonal/surgical remission rates, Ki67 index, and p53 expression between mutated and non-mutated somatotropinomas patients.  PTTG  overexpression (RQ mean=10.6, min=4.39, max=11.9) and  AIP  underexpression (RQ mean=0.56, min=0.46-max=0.92) were found in virtually all cases without a statistically significant relationship with clinical and biological tumor features. No patients exhibited somatic or germline pathogenic  AIP  mutations. In conclusion, mutations in  GNAS  and abnormal  PTTG  and  AIP  expression had no impact on tumor features and treatment outcomes in this cohort. Our data support some previous studies and point to the need for further investigations, probably involving epigenetic and transcriptome analysis, to improve our understanding of pituitary tumor behavior.

brazilian journal of medical and biological research

Study of major genetic factors involved in pituitary tumorigenesis and their impact on clinical and biological characteristics of sporadic somatotropinomas and non-functioning pituitary adenomas