Pangenomic Classification of Pituitary Neuroendocrine Tumors

Cancer Cell. 2020 Jan 13;37(1):123-134.e5. doi: 10.1016/j.ccell.2019.11.002. Epub 2019 Dec 26.


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.

Keywords: chromosome alterations; exome; genomic; methylome; miRNome; outcome; pituitary neuroendocrine tumors (PitNETs); transcriptome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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 / diagnosis*
  • Neuroendocrine Tumors / genetics*
  • Neuroendocrine Tumors / pathology
  • Pituitary Gland / metabolism
  • Pituitary Neoplasms / diagnosis*
  • Pituitary Neoplasms / genetics*
  • Pituitary Neoplasms / pathology
  • Prognosis
  • Transcriptome
  • Ubiquitin Thiolesterase / metabolism
  • Young Adult


  • Endosomal Sorting Complexes Required for Transport
  • Endopeptidases
  • USP8 protein, human
  • Ubiquitin Thiolesterase