The role of methylation in pituitary neuroendocrine tumors current insights and emerging perspectives.

Pituitary Neuroendocrine Tumors (PitNETs) are the most frequently diagnosed intracranial neoplasms in adults. The World Health Organization's 2022 fifth edition classification of pituitary neuroendocrine tumours (PitNETs) maintains an immunohistochemistry based taxonomy that places molecular biology at the centre of diagnosis. This framework provides a solid basis for subtype classification and therapy development. Methylation, defined as the transfer of a methyl group (CH₃) to DNA bases, histone side chains, or RNA nucleotides, is an epigenetic modification that has emerged as a key mechanism in neoplastic transformation. In this review, we synthesise current knowledge on histone, DNA, and RNA methylation in pituitary tumourigenesis, describing their distinct roles and mutual molecular crosstalk. By examining how these epigenetic modifications promote tumour initiation and progression, we assess their potential as drug targets and their translational applicability. Our objective is to propose new research directions and precision treatment strategies that exploit methylation related vulnerabilities, with the goal of improving clinical outcomes for patients with PitNETs.