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Pangenomic Classification of Pituitary Neuroendocrine Tumors.

Authors :
Neou M
Villa C
Armignacco R
Jouinot A
Raffin-Sanson ML
Septier A
Letourneur F
Diry S
Diedisheim M
Izac B
Gaspar C
Perlemoine K
Verjus V
Bernier M
Boulin A
Emile JF
Bertagna X
Jaffrezic F
Laloe D
Baussart B
Bertherat J
Gaillard S
AssiƩ G
Source :
Cancer cell [Cancer Cell] 2020 Jan 13; Vol. 37 (1), pp. 123-134.e5. Date of Electronic Publication: 2019 Dec 26.
Publication Year :
2020

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.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1878-3686
Volume :
37
Issue :
1
Database :
MEDLINE
Journal :
Cancer cell
Publication Type :
Academic Journal
Accession number :
31883967
Full Text :
https://doi.org/10.1016/j.ccell.2019.11.002