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Publications

Journal Article Ahead of print

PubMed: 42151365 DOI: 10.1038/s43856-026-01615-5

Trametinib for multiple non-ossifying fibromas due to KRAS mosaic mutations: two case reports.

Commun Med (Lond)

Authors: Marie Vincent, Soizic Tiriau, Marine Fouillet-Desjonqueres, Alicia Besson, Wassim Ouchetto, Sébastien Barbarot, Bertrand Isidor, Aymeric Rouchaud, Geneviève Baujat, Pierre Vabres, Patrick Edery, Marion Delous, Massimiliano Rossi

Affiliations

  • Service de Génétique Médicale, CHU Nantes, Nantes, France.
  • Institut du thorax, INSERM, CNRS, UNIV, Nantes, France.
  • Service de Pédiatrie-Spécialités, CHU Nantes, Nantes, France.
  • Service de Néphrologie-Rhumatologie-Dermatologie Pédiatriques, Hospices Civils de, Lyon, France.
  • Centre de référence des Maladies Osseuses Constitutionnelles, Hospices Civils de, Lyon, France.
  • Université Claude Bernard Lyon 1, CNRS, INSERM, Centre de Recherche en Neurosciences de Lyon CRNL U1028 UMR5292, GENDEV, Bron, France.
  • Service de Dermatologie, CHU Nantes, Nantes, France.
  • Service de Génétique Médicale, CHU Nantes, Nantes, France.
  • Institut du thorax, INSERM, CNRS, UNIV, Nantes, France.
  • Service d'Imagerie Médicale, Hospices Civils de, Lyon, France.
  • Service de Génétique Médicale, Centre de Référence des Maladies Osseuses Constitutionnelles, Hôpital Necker-Enfants Malades, APHP, Paris, France.
  • Service de Dermatologie, CHU Dijon Bourgogne, Dijon, France.
  • Service de Génétique, Hospices Civils de, Lyon, France.

Abstract

BACKGROUND

KRAS mosaic activating variants are the main cause of non-ossifying fibromas (NOFs), the most common benign lesion of the growing skeleton. Multifocal NOFs cause bone fragility, and no specific treatment is currently available.

METHODS

We report two children, carrying mosaic KRAS variants (p.G13D and p.A146T), presenting with oculoectodermal syndrome and recurrent fractures due to progressive polyostotic NOFs. To assess the impact of these mutations on KRAS function, we conducted transient KRAS overexpression in HEK293 cells and then tested the effect of the MEK-inhibitor trametinib at the cellular level.

RESULTS

We show that trametinib yields, in vitro, significant reduction of RAS-pathway hyperactivation induced by the two KRAS variants and, in vivo, remarkable clinical and radiological improvement with no recurrence of fractures and reossification of NOFs under treatment; resurgence of lesions is observed one year after stopping treatment.

CONCLUSIONS

Hence, trametinib constitutes a promising precision therapeutic approach for severe KRAS-related NOFs.

MeSH

Fibroma, Fibroma, Ossifying, Therapeutics, Mutation