{
  "abstract": "BACKGROUND: Aggressive evolution of PitNETs is rare; metastatic spread is even more. Defining aggressiveness and malignancy is challenging, subsequently hard to predict, and to understand. The aim was to provide a molecular definition of aggressiveness using genomic approaches. METHODS: PitNETs from 206 patients were included. Associations between 9 clinicopathological features of aggressiveness and PitNETs' omics were explored. Omics included transcriptome, DNA methylation, chromosomal alterations, and mutations. Clonal tumor evolution was monitored in 7 patients. RESULTS: Among the 9 clinicopathological features of aggressiveness, only rapid progression, progression after radiotherapy, Ki67/MIB1 proliferation index ≥10%, temozolomide treatment, metastases, and specific death were associated with specific omics signatures, while tumour maximal diameter ≥40 mm, cavernous, and sphenoid invasion were not. The omic signatures associated with these features of aggressiveness overlapped but remained distinct between corticotroph and mammo-somato-thyrotroph lineages. For each lineage, a common signature of aggressiveness was identified, associating a proliferative transcriptome signature and DNA hypermethylation. Alterations in specific genes were associated with aggressive features, including a novel PitNET gene, LRP1B, and known cancer genes (TP53, CDKN2A), while USP8 and GNAS alterations were not. Integration of gene alterations with methylome and transcriptome signatures isolated a subset of molecularly aggressive PitNETs. Molecular signatures were stable during the course of the disease, despite evolution toward aggressiveness and potential clonal divergence. CONCLUSION: This systematic analysis of clinicopathological features of aggressiveness using an integrated multiomic approach establishes a histomolecular definition of aggressiveness in PitNETs. Prospective cohort studies are needed to validate these molecular signatures and establish their prognostic value.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 33,
  "authors": [
    {
      "name": "Nesrine Benanteur"
    },
    {
      "name": "Chiara Villa"
    },
    {
      "name": "Fabio Bioletto"
    },
    {
      "name": "Maria Francesca Birtolo"
    },
    {
      "name": "Daniel de Murat"
    },
    {
      "name": "Julien Masliah-Planchon"
    },
    {
      "name": "Victor Gravrand"
    },
    {
      "name": "Inès Lebib"
    },
    {
      "name": "Mounia Benkhellat"
    },
    {
      "name": "Robin Boezennec"
    },
    {
      "name": "Stéphanie Allassonnière"
    },
    {
      "name": "Franck Letourneur"
    },
    {
      "name": "Yoann Martin"
    },
    {
      "name": "Fidéline Bonnet Serrano"
    },
    {
      "name": "Julian Jacob"
    },
    {
      "name": "Valentin Calugaru"
    },
    {
      "name": "Maxime Barat"
    },
    {
      "name": "Anthony Dohan"
    },
    {
      "name": "Jennifer Arrondeau"
    },
    {
      "name": "Olivier Huillard"
    },
    {
      "name": "Marie-Laure Raffin-Sanson"
    },
    {
      "name": "Jean François Emile"
    },
    {
      "name": "Gérald Raverot"
    },
    {
      "name": "Rossella Libé"
    },
    {
      "name": "Laurence Guignat"
    },
    {
      "name": "Cyril Garcia"
    },
    {
      "name": "Lionel Groussin"
    },
    {
      "name": "Xavier Bertagna"
    },
    {
      "name": "Stephan Gaillard"
    },
    {
      "name": "Jérôme Bertherat"
    },
    {
      "name": "Anne Jouinot"
    },
    {
      "name": "Bertrand Baussart"
    },
    {
      "name": "Guillaume Assié"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8pqdmeg86ddgw.bib",
  "cited_by": 4,
  "doi": "10.1093/neuonc/noag074",
  "fulltext_url": null,
  "id": "8pqdmeg86ddgw",
  "issns": [
    "1522-8517",
    "1523-5866"
  ],
  "landing_url": "https://hal.science/hal-05851595v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2712|Pituitary Gland Disorders and Treatments"
    ]
  ],
  "openalex": "W7152562341",
  "pdf_url": null,
  "pmcid": null,
  "pmid": "41955313",
  "published": "2026-11-04",
  "publisher": "Oxford University Press (OUP)",
  "ris": "https://research.draconitic.com/paper/8pqdmeg86ddgw.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:20:53Z",
      "native_id": "hal-05851595",
      "source": "hal",
      "url": "https://hal.science/hal-05851595v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2712|Pituitary Gland Disorders and Treatments",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "Genomic characterization of aggressiveness in pituitary neuroendocrine tumors",
  "title_text": "Genomic characterization of aggressiveness in pituitary neuroendocrine tumors",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:20:44Z",
  "url": "https://research.draconitic.com/paper/8pqdmeg86ddgw",
  "venue": "Neuro-Oncology",
  "versions": []
}