Abstract
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.
Highlights
Pituitary adenomas are mostly sporadic and result from genetic mutations in a single cell involving overexpression of oncogenes, inactivation of tumor suppressor genes, and alterations of transcription factors regulating cell growth and differentiation [1,2]
Proto-oncogenes GNAS, pituitary tumor transforming gene (PTTG), and tumor suppressor gene aryl hydrocarbon receptor interacting protein (AIP) are the most prominent genetic factors involved in pituitary tumorigenesis and have been implicated in the development of somatotropinomas and non-functioning pituitary adenomas (NFPA) [2]
The present study evaluated clinical, laboratory, and GNAS, AIP, and PTTG molecular data of 62 apparently sporadic pituitary adenomas followed in a single endocrine tertiary-referral center
Summary
Pituitary adenomas are mostly sporadic and result from genetic mutations in a single cell involving overexpression of oncogenes, inactivation of tumor suppressor genes, and alterations of transcription factors regulating cell growth and differentiation [1,2]. Proto-oncogenes GNAS (guanine nucleotide-binding protein, alpha stimulating), PTTG (pituitary tumor-transforming gene 1), and tumor suppressor gene AIP (aryl-hydrocarbon receptor-interacting protein) are the most prominent genetic factors involved in pituitary tumorigenesis and have been implicated in the development of somatotropinomas and non-functioning pituitary adenomas (NFPA) [2]. We assessed the presence of GNAS and AIP mutations as well as altered gene expressions of AIP and PTTG in sporadic somatotropinomas and NFPA patients admitted to a single endocrine tertiary-referral center. The importance of these genetic factors, Ki-67 cell proliferation marker, and p53 on the prognosis of pituitary adenomas was evaluated. In silico predictions were performed only for rare variants using NetGene (http://www.cbs.dtu.dk/services/Net Gene2/) and Human Splicing Finder (HSF, www.umd. be/HSF3)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
