The Role of Epigenetics in the Pathogenesis of Human Pituitary Adenomas

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Ursula Kaiser, MD

Pituitary tumors are among the most commonly occurring neoplasms of the central nervous system, comprising approximately 15% of intracranial tumors. Although typically benign, they cause significant morbidity through mass effects and/or the inappropriate secretion of pituitary hormones, resulting in loss of vision, infertility, growth disorders, and metabolic disturbances.

The causes of pituitary tumor formation have been studied extensively, but the mechanisms involved in pituitary cell transformation remain elusive. Hormones and growth factors that modulate normal pituitary development and endocrine activity have been implicated in pituitary tumor growth, but do not appear to be the initiating cause. Mutations of tumor suppressor genes or oncogenes, as seen in more common cancers, do not seem to play an importantrole in the majority of pituitary adenomas. Recent evidence from Dr. Kaiser’s lab suggests that epigenetic histone modifications may play important roles in pituitary tumor pathogenesis.

Epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence. Dr. Kaiser and her team plans to leverage the unique resources of the Brigham & Women’s Hospital Pituitary/Neuroendocrine Center and the associated comprehensive pituitary tumor tissue bank to further investigate the contributions of such epigenetic histone modifications to the formation of pituitary adenomas. Epigenetic studies in these tumors can lead not only to new insights into the pathophysiology of pituitary adenomas, but can in turn provide insights into the mechanisms underlying other cancers. These studies are also likely to help us understand why these adenomas do not progress tomalignant carcinomas in most cases, and may help us understand pathways that restrain the progression of pituitary tumors from benign to malignant neoplasms, which may have significantly broader implications for other tumor types.