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Pangenomic Classification of Pituitary Neuroendocrine Tumors.
- 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.)
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Cell Lineage
Chromosome Aberrations
DNA Methylation
Endopeptidases metabolism
Endosomal Sorting Complexes Required for Transport metabolism
Epigenesis, Genetic
Epigenome
Exome
Female
Humans
Male
Middle Aged
Mutation
Neoplasm Invasiveness
Neuroendocrine Tumors pathology
Pituitary Gland metabolism
Pituitary Neoplasms pathology
Prognosis
Transcriptome
Ubiquitin Thiolesterase metabolism
Young Adult
Neuroendocrine Tumors diagnosis
Neuroendocrine Tumors genetics
Pituitary Neoplasms diagnosis
Pituitary Neoplasms genetics
Subjects
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