Molecular genetic abnormalities in ACTH-secreting pituitary tumors (corticotropinomas): fundamental research and prospects for use in clinical practice

Abstract

In recent years, a large number of studies have been carried out to research molecular genetic abnormalities in ACTH-­secreting pituitary tumors. This review presents a comprehensive analysis of exome studies results (germline and somatic mutations, chromosomal abnormalities in corticotropinomas which developed as part of hereditary syndromes MEN 1, 2, 4, DICER1, Carney complex etc., and isolated tumors, respectively) and transcriptome (specific genes expression profiles in hormonally active and inactive corticotropinomas, regulation of cell cycles and signal pathways). Modern technologies (next-generation sequencing — NGS) allow us to study the state of the microRNAome, DNA methylome and inactive chromatin sites, in particular using RNA sequencing. Thus, a wide range of fundamental studies is shown, the results of which allow us to identify and comprehend the key previously known and new pathogenesis mechanisms and biomarkers of corticotropinomas. The characteristics of the most promising molecular genetic factors that can be used in clinical practice for screening and earlier diagnosis of hereditary syndromes and isolated corticotropinomas, differential diagnosis of various forms of endogenous hypercorticism, sensitivity to existing and potential therapies and personalized outcome determination of Cushing`s disease.