Genetic characterization of a series of pituitary tumors

Abstract

Pituitary neuroendocrine tumors (PitNETs) are common intracranial neoplasms that, despite their mostly benign nature, can cause significant morbidity due to hormone dysregulation and local mass effects. Recent research has revealed key genetic and epigenetic mechanisms driving PitNET development; however, many molecular features remain poorly defined, particularly across less-studied subtypes. This study aimed to investigate the genetic alterations underlying diverse PitNETs by screening for mutations in candidate genes frequently implicated in pituitary tumorigenesis. Specifically, the study focused on GNAS, USP8, BRAF, and SF3B1, which are known to influence pathways such as cAMP signaling, EGFR regulation, MAPK activation, and RNA splicing. A total of 153 formalin-fixed, paraffin-embedded (FFPE) tumor samples representing multiple PitNET subtypes were analyzed is this study. Genomic DNA was extracted and subjected to polymerase chain reaction (PCR) amplification, ExoSAP-based purification, and Sanger sequencing to detect mutations in the target regions. Clinical and pathological data, including patient demographics, tumor size, invasiveness, hormone secretion profile, and proliferative indices, were integrated to assess potential genotype-phenotype correlations. The results revealed recurrent GNAS mutations in somatotroph tumors, with a prevalence (30,7%) consistent with that in the previous literature. USP8 mutations were detected exclusively in corticotroph tumors (56,3%), whereas BRAF and SF3B1 alterations were absent in the entire cohort. No significant associations were observed between the mutational status and clinical features, such as remission rates or proliferative indices. By combining molecular screening with clinicopathological data, this study helps to clarify the genetic profile of PitNETs and confirms that recurrent mutations are frequent and occur in a subtype-specific manner, particularly GNAS in somatotroph tumors and USP8 in corticotroph tumors. Although no significant genotype-phenotype associations were found, the results contribute to a better description of PitNET heterogeneity and provide a basis for future work to further explore their biological relevance.