Pangenomic Classification of Pituitary Neuroendocrine Tumors.
Cancer Cell
; 37(1): 123-134.e5, 2020 01 13.
Article
em En
| MEDLINE
| ID: mdl-31883967
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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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Hipofisárias
/
Tumores Neuroendócrinos
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article