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Journal Articles Cancer Cell Year : 2020

Pangenomic classification of pituitary neuroendocrine tumors

Jean-François Emile

Abstract

Pituitary neuroendocrine tumors (PitNETs) are common, with five main histological subtypes: lactotroph, somatotroph, and thyrotroph (POU1F1/PIT1 lineage); corticotroph (TBX19/TPIT lineage); and gonadotroph (NR5A1/SF1 lineage). We report a comprehensive pangenomic classification of PitNETs. PitNETs from POU1F1/PIT1 lineage showed an epigenetic signature of diffuse DNA hypomethylation, with transposable elements expression and chromosomal instability (except for GNAS-mutated somatotrophs). In TPIT lineage, corticotrophs were divided into three classes: the USP8-mutated with overt secretion, the USP8-wild-type with increased invasiveness and increased epithelial-mesenchymal transition, and the large silent tumors with gonadotroph transdifferentiation. Unexpected expression of gonadotroph markers was also found in GNAS-wild-type somatotrophs (SF1 expression), challenging the current definition of SF1/gonadotroph lineage. This classification improves our understanding and affects the clinical stratification of patients with PitNETs.
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Dates and versions

hal-02441511 , version 1 (21-07-2022)

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Attribution - NonCommercial

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Mario Neou, Chiara Villa, Roberta Armignacco, A. Jouinot, Marie-Laure Raffin-Sanson, et al.. Pangenomic classification of pituitary neuroendocrine tumors. Cancer Cell, 2020, 37 (1), pp.123-134. ⟨10.1016/j.ccell.2019.11.002⟩. ⟨hal-02441511⟩
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