AUTHOR=Chang Mengqi , Yang Chengxian , Bao Xinjie , Wang Renzhi 

TITLE=Genetic and Epigenetic Causes of Pituitary Adenomas

JOURNAL=Frontiers in Endocrinology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.596554

DOI=10.3389/fendo.2020.596554

ISSN=1664-2392

ABSTRACT=<p>Pituitary adenomas (PAs) can be classified as non-secreting adenomas, somatotroph adenomas, corticotroph adenomas, lactotroph adenomas, and thyrotroph adenomas. Substantial advances have been made in our knowledge of the pathobiology of PAs. To obtain a comprehensive understanding of the molecular biological characteristics of different types of PAs, we reviewed the important advances that have been made involving genetic and epigenetic variation, comprising genetic mutations, chromosome number variations, DNA methylation, microRNA regulation, and transcription factor regulation. Classical tumor predisposition syndromes include multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4) syndromes, Carney complex, and X-LAG syndromes. PAs have also been described in association with succinate dehydrogenase-related familial PA, neurofibromatosis type 1, and von Hippel–Lindau, DICER1, and Lynch syndromes. Patients with aryl hydrocarbon receptor-interacting protein (<italic>AIP</italic>) mutations often present with pituitary gigantism, either in familial or sporadic adenomas. In contrast, guanine nucleotide-binding protein G(s) subunit alpha (<italic>GNAS</italic>) and G protein-coupled receptor 101 (<italic>GPR101</italic>) mutations can lead to excess growth hormone. Moreover, the deubiquitinase gene <italic>USP8</italic>, <italic>USP48</italic>, and <italic>BRAF</italic> mutations are associated with adrenocorticotropic hormone production. In this review, we describe the genetic and epigenetic landscape of PAs and summarize novel insights into the regulation of pituitary tumorigenesis.</p>