Genetic and Epigenetic Pathogenesis of Acromegaly

SIMPLE SUMMARY: Various genetic and epigenetic factors are involved in the pathogenesis of somatotroph tumors. Although GNAS mutations are the most prevalent cause of somatotroph tumors, the cause of half of all pathogenesis occurrences remains unclarified. However, recent findings including the pangenomic analysis, such as genome, transcriptome, and methylome approaches, and histological characteristics of pituitary tumors, the involvement of AIP and GPR101, the mechanisms of genomic instability, and possible involvement of miRNAs have gradually unveiled the whole landscape of underlying mechanisms of somatotroph tumors. In this review, we will focus on the recent advances in the pathogenesis of somatotroph tumors. ABSTRACT: Acromegaly is caused by excessive secretion of GH and IGF-I mostly from somatotroph tumors. Various genetic and epigenetic factors are involved in the pathogenesis of somatotroph tumors. While somatic mutations of GNAS are the most prevalent cause of somatotroph tumors, germline mutations in various genes (AIP, PRKAR1A, GPR101, GNAS, MEN1, CDKN1B, SDHx, MAX) are also known as the cause of somatotroph tumors. Moreover, recent findings based on multiple perspectives of the pangenomic approach including genome, transcriptome, and methylome analyses, histological characterization, genomic instability, and possible involvement of miRNAs have gradually unveiled the whole landscape of the underlying mechanisms of somatotroph tumors. In this review, we will focus on the recent advances in genetic and epigenetic pathogenesis of somatotroph tumors.