2026/04/01 by Borbála Szabó, Attila Patócs, Henriett Butz · 1 voice
Medicine · Biochemistry, Genetics and Molecular Biology · #Pituitary Gland Disorders and Treatments #Epigenetics and DNA Methylation #Glioma Diagnosis and Treatment
paper · doi:10.1530/erc-26-0030
openalex publication_date 2026/04/01 · openalex created_date 2026/04/16 · openalex updated_date 2026/07/16
Apart from a few subtype-specific genetic alterations, pituitary neuroendocrine tumours (PitNETs) exhibit a limited number of recurrent genetic alterations, emphasising the pivotal role of epigenetic dysregulation in their pathogenesis. DNA methylation has been widely investigated in PitNETs and has been associated with tumour subtypes, tumour biology, and clinical outcome. Most studies use methodologies that cannot distinguish between methylation and active demethylation. DNA methylation is a dynamic and reversible process, governed by a tightly regulated cycle involving 5-methylcytosine and its oxidised derivatives - particularly 5-hydroxymethylcytosine - which have opposing effects on gene regulation. Failure to resolve these cytosine modifications may, therefore, obscure biologically relevant mechanisms and may contribute to inconsistent findings across studies. This mini-review critically examines the DNA methylation-demethylation cycle in PitNETs, discusses the challenges of accurately detecting cytosine modifications, and summarises the emerging evidence, linking altered demethylation dynamics to tumour differentiation, proliferation, and aggressiveness. We also highlight the therapeutic relevance of targeting epigenetic regulators, such as DNA methyltransferases, TET enzymes, and associated co-factors, and review data supporting both traditional epigenetic drugs and repurposed agents. Finally, we discuss future perspectives, including the potential of liquid biopsy-based methylation profiling and advanced sequencing technologies to improve PitNET classification, prognostication, and therapeutic stratification in the near future.