Genetic and Epigenetic Pathogenesis of Acromegaly

Masaaki Yamamoto; Yutaka Takahashi

doi:10.3390/cancers14163861

Genetic and Epigenetic Pathogenesis of Acromegaly

Cancers (Basel). 2022 Aug 10;14(16):3861. doi: 10.3390/cancers14163861.

Authors

Masaaki Yamamoto¹, Yutaka Takahashi^{1

2}

Affiliations

¹ Division of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
² Department of Diabetes and Endocrinology, Nara Medical University, Kashihara 634-8521, Japan.

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.

Keywords: FIPA; GNAS; acromegaly; miRNA; somatotroph tumors.

Publication types

Review

Grants and funding

This work was supported by the Ministry of Health, Labor and Welfare, Japan (Grants-in-Aid for Scientific Research on Hypothalamo-hypophyseal Disorders and Grants-in-Aid for Scientific Research on Endocrine Syndrome with Sexual Differentiation and Maturation).