Evidence map›Paper›PMID 41955313›Full record

ArticleNeuro-oncology2026

Genomic characterization of aggressiveness in pituitary neuroendocrine tumors.

Nesrine Benanteur, Chiara Villa, Fabio Bioletto, Maria Francesca Birtolo, Daniel De Murat, Julien Masliah-Planchon, Victor Gravrand, Inès Lebib, Mounia Benkhellat, Robin Boezennec and 23 more

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In one paragraph

Article in Neuro-oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

33 authors.

Nesrine BenanteurCNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris, France.ORCID 0009-0008-2758-5500
Chiara VillaCNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris, France.ORCID 0000-0001-6245-4487
Fabio BiolettoCNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris, France.ORCID 0000-0001-7550-7023
Maria Francesca BirtoloCNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris, France.ORCID 0000-0001-8100-8394
Daniel De MuratCNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris, France.
Julien Masliah-PlanchonDepartment of Diagnostic and Theranostic Medicine, Somatic Genetics Unit, Institut Curie, Paris-Science Lettres University, Paris, France.ORCID 0000-0002-5596-3926
Victor GravrandCNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris, France.
Inès LebibCNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris, France.
Mounia BenkhellatCNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris, France.ORCID 0009-0002-2502-8221
Robin BoezennecCNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris, France.ORCID 0009-0008-5016-4413
Stéphanie AllassonnièreUniversité Paris Cité, Unité Mixte de Recherche S1138, Institut National de Recherche en Sciences et Technologies du Numérique, Sorbonne University, Paris, France.ORCID 0000-0002-5692-4945
Franck LetourneurINSERM U1016, Institut Cochin, Plate-Forme Séquençage et Génomique (Genom'IC), Paris, France.ORCID 0000-0001-9465-4774
Yoann MartinCNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris, France.
Fidéline Bonnet SerranoCNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris, France.ORCID 0000-0002-6628-8807
Julian JacobDepartment of Radiation Oncology, Hôpital La Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.ORCID 0000-0003-3156-475X
Valentin CalugaruDepartment of Radiation Oncology, Paris/Saint-Cloud/Orsay, Institut Curie, PSL Research University, Paris, France.ORCID 0000-0002-7156-9750
Maxime BaratCNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris, France.ORCID 0000-0002-0360-0875
Anthony DohanCNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris, France.ORCID 0000-0002-8732-5603
Jennifer ArrondeauDepartment of Clinical Oncology, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.ORCID 0009-0003-9508-8956
Olivier HuillardMedical Oncology Department, Université Paris Cité, Institut du Cancer Paris CARPEM, AP-HP, Hôpital Cochin-Port Royal, Paris, France.ORCID 0000-0001-9764-0845
Marie-Laure Raffin-SansonDepartment of Endocrinology, Diabetology, and Nutrition, Ambroise Paré University Hospital, Assistance Publique-Hôpitaux de Paris, Boulogne Billancourt, France.
Jean François EmileDepartment of Pathology, Hôpital Ambroise Paré, Assistance Publique-Hôpitaux de Paris, Boulogne-Billancourt, France.ORCID 0000-0002-6073-4466
Gérald RaverotCancer Research Center of Lyon, Inserm U1052, CNRS UMR5286, Lyon 1 University, Lyon, France.ORCID 0000-0002-9517-338X
Rossella LibéCNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris, France.ORCID 0000-0003-2881-6362
Laurence GuignatDepartment of Endocrinology, Hôpital Cochin, Reference and Competence Center for Rare Adrenal Diseases and Rare Pituitary Diseases, Assistance Publique-Hôpitaux de Paris, Paris, France.ORCID 0000-0003-2782-5750
Cyril GarciaService D'Endocrinologie, Hôpital National D'Instruction des Armées Bégin, Saint-Mandé, France.ORCID 0000-0001-6833-3731
Lionel GroussinCNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris, France.ORCID 0000-0003-1476-475X
Xavier BertagnaCNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris, France.
Stephan GaillardCNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris, France.ORCID 0009-0008-6979-0991
Jérôme BertheratCNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris, France.ORCID 0000-0003-2551-3008
Anne JouinotCNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris, France.ORCID 0000-0002-7922-2065
Bertrand BaussartCNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris, France.ORCID 0000-0003-0735-8278
Guillaume AssiéCNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris, France.ORCID 0000-0001-9590-0906

Funding

Assistance Publique des Hôpitaux de Paris (France) and Université Paris CitéCancer Research for Personalized MedicineFonds de dotation pour la Recherche et l'Innovation en Endocrinologie et Maladies Métaboliques
6 · The paper itself

Abstract

backgroundAggressive 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.

methodsPitNETs 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.

resultsAmong 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.

conclusionThis 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.

Indexed as

Biomarkers, TumorGenomicsNeuroendocrine TumorsPituitary NeoplasmsAdultAgedDNA MethylationFemaleFollow-Up StudiesGene Expression ProfilingHumansMaleMiddle AgedMutationPrognosisTranscriptomeBiomarkers, TumorcarcinomagenomicsLRP1BPitNETsprognosis

Identifiers

PMID41955313
PMCPMC13550688

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