Abstract
The genetic landscape of pituitary adenomas (PAs) is diverse and many of the identified cases remain of unclear pathogenetic mechanism. Germline genetic defects account for a small percentage of all patients and may present in the context of relevant family history. Defects in AIP (mutated in Familial Isolated Pituitary Adenoma syndrome or FIPA), MEN1 (coding for menin, mutated in Multiple Endocrine Neoplasia type 1 or MEN 1), PRKAR1A (mutated in Carney complex), GPR101 (involved in X-Linked Acrogigantism or X-LAG), and SDHx (mutated in the so called “3 P association” of PAs with pheochromocytomas and paragangliomas or 3PAs) account for the most common familial syndromes associated with PAs. Tumor genetic defects in USP8, GNAS, USP48 and BRAF are some of the commonly encountered tissue-specific changes and may explain a larger percentage of the developed tumors. Somatic (at the tumor level) genomic changes, copy number variations (CNVs), epigenetic modifications, and differential expression of miRNAs, add to the variable genetic background of PAs.
Highlights
IntroductionPituitary adenomas (PAs) are common lesions in the adult population presenting in 15–20% of cadavers or radiologic findings and constitute approximately 10% of all intracranial tumors [1,2]
Pituitary adenomas (PAs) are common lesions in the adult population presenting in 15–20% of cadavers or radiologic findings and constitute approximately 10% of all intracranial tumors [1,2].PAs are rarer in the pediatric population identified in 0.2% of children undergoing brain imaging [3]. most of the identified PAs are incidental findings without the need for intervention, some may present as clinically significant because they secrete hormones or cause symptoms from compression or invasion of surrounding tissues [4].The etiology of PAs is diverse, and more than half of them do not have an identified genetic cause.In certain cases, germline or somatic genetic defects are associated with the formation of PAs
Additional genetic changes found in PAs, such as copy number variations (CNVs), methylation changes and miRNA abnormalities have been investigated as being potentially involved in the pathogenesis, presentation and behavior of these tumors, especially with regard to aggressiveness and response to treatment
Summary
Pituitary adenomas (PAs) are common lesions in the adult population presenting in 15–20% of cadavers or radiologic findings and constitute approximately 10% of all intracranial tumors [1,2]. Most of the identified PAs are incidental findings without the need for intervention, some may present as clinically significant because they secrete hormones or cause symptoms from compression or invasion of surrounding tissues [4]. This review focuses on the current knowledge of the genetic findings in PAs at the germline (Tables 1 and 2) and somatic (Table 3) level. Additional information on the genomic profile of PAs can derive from expression studies, methylation analyses and miRNA changes, which are briefly mentioned in the current review. Alpha regulatory subunit of PKA; inactivation of PRKAR1A leads to dissociation of the regulatory from the catalytic subunit and aberrant PKA activity
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