| Literature DB >> 31883967 |
Mario Neou1, Chiara Villa2, Roberta Armignacco1, Anne Jouinot1, Marie-Laure Raffin-Sanson3, Amandine Septier1, Franck Letourneur4, Ségolène Diry1, Marc Diedisheim5, Brigitte Izac4, Cassandra Gaspar6, Karine Perlemoine1, Victoria Verjus1, Michèle Bernier7, Anne Boulin8, Jean-François Emile9, Xavier Bertagna10, Florence Jaffrezic11, Denis Laloe11, Bertrand Baussart12, Jérôme Bertherat10, Stephan Gaillard12, Guillaume Assié13.
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.Entities:
Keywords: chromosome alterations; exome; genomic; methylome; miRNome; outcome; pituitary neuroendocrine tumors (PitNETs); transcriptome
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Year: 2019 PMID： 31883967 DOI： 10.1016/j.ccell.2019.11.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743