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Genomics and Epigenomics of Pituitary Tumors: What Do Pathologists Need to Know?

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Abstract

Molecular pathology has advanced our understanding of many tumors and offers opportunities to identify novel therapies. In the pituitary, the field has uncovered several genetic mutations that predispose to pituitary neuroendocrine tumor (PitNET) development, including MEN1, CDKN1B, PRKRIα, AIP, GPR101, and other more rare events; however, these genes are only rarely mutated in sporadic PitNETs. Recurrent genetic events in sporadic PitNETs include GNAS mutations in a subset of somatotroph tumors and ubiquitin-specific peptidase mutations (e.g., USP8, USP48) in some corticotroph tumors; to date, neither of these has resulted in altered management, and instead, the prognosis and management of PitNETs still rely more on cell type and subtype as well as local growth that determines surgical resectability. In contrast, craniopharyngiomas have either CTNNB1 or BRAFV600E mutations that correlate with adamantinomatous or papillary morphology, respectively; the latter offers the opportunity for targeted therapy. DICER1 mutations are found in patients with pituitary blastoma. Epigenetic changes are implicated in the pathogenesis of the more common sporadic pituitary neoplasms including the majority of PitNETs and tumors of pituicytes.

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Authors and Affiliations

  1. Department of Pathology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio, USA

    Sylvia L. Asa

  2. Department of Pathology, University Health Network, Toronto, ON, Canada

    Sylvia L. Asa & Ozgur Mete

  3. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

    Ozgur Mete

  4. Department of Medicine, University Health Network and University of Toronto, Toronto, ON, Canada

    Shereen Ezzat

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Asa, S.L., Mete, O. & Ezzat, S. Genomics and Epigenomics of Pituitary Tumors: What Do Pathologists Need to Know?. Endocr Pathol 32, 3–16 (2021). https://doi.org/10.1007/s12022-021-09663-4

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