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Wnt/β-catenin activation by mutually exclusive FBXW11 and CTNNB1 hotspot mutations drives salivary basal cell adenoma

Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) of the salivary gland are rare tumours that can be difficult to distinguish from each other and other salivary gland tumour subtypes. Using next-generation sequencing, we identify a recurrent FBXW11 missense mutation (p.F517S) in BCA that...

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Main Authors: Wong, Kim (Author) , Bishop, Justin A. (Author) , Weinreb, Ilan (Author) , Motta, Marialetizia (Author) , Del Castillo Velasco-Herrera, Martin (Author) , Bellacchio, Emanuele (Author) , Ferreira, Ingrid (Author) , van der Weyden, Louise (Author) , Boccacino, Jacqueline M. (Author) , Lauri, Antonella (Author) , Rotundo, Giovannina (Author) , Ciolfi, Andrea (Author) , Cheema, Saamin (Author) , Olvera-León, Rebeca (Author) , Offord, Victoria (Author) , Droop, Alastair (Author) , Vermes, Ian (Author) , Allgäuer, Michael (Author) , Hyrcza, Martin (Author) , Anderson, Elizabeth (Author) , Smith, Katie (Author) , de Saint Aubain, Nicolas (Author) , Mogler, Carolin (Author) , Stenzinger, Albrecht (Author) , Arends, Mark J. (Author) , Brenn, Thomas (Author) , Tartaglia, Marco (Author) , Adams, David J. (Author)
Format: Article (Journal)
Language:English
Published: 19 May 2025
In: Nature Communications
Year: 2025, Volume: 16, Pages: 1-18
ISSN:2041-1723
DOI:10.1038/s41467-025-59871-3
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-025-59871-3
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-025-59871-3
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Author Notes:Kim Wong, Justin A. Bishop, Ilan Weinreb, Marialetizia Motta, Martin Del Castillo Velasco-Herrera, Emanuele Bellacchio, Ingrid Ferreira, Louise van der Weyden, Jacqueline M. Boccacino, Antonella Lauri, Giovannina Rotundo, Andrea Ciolfi, Saamin Cheema, Rebeca Olvera-León, Victoria Offord, Alastair Droop, Ian Vermes, Michael Allgäuer, Martin Hyrcza, Elizabeth Anderson, Katie Smith, Nicolas de Saint Aubain, Carolin Mogler, Albrecht Stenzinger, Mark J. Arends, Thomas Brenn, Marco Tartaglia & David J. Adams
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Summary:Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) of the salivary gland are rare tumours that can be difficult to distinguish from each other and other salivary gland tumour subtypes. Using next-generation sequencing, we identify a recurrent FBXW11 missense mutation (p.F517S) in BCA that is mutually exclusive with the previously reported CTNNB1 p.I35T gain-of-function (GoF) mutation with these mutations collectively accounting for 94% of BCAs. In vitro, mutant FBXW11 is characterised by defective binding to β-catenin and higher protein levels within the nucleus. This is consistent with the increased nuclear expression of β-catenin and activation of the Wnt/β-catenin pathway. The genomic profiles of BCAC are distinct from BCA, with hotspot DICER1 and HRAS mutations and putative driver mutations affecting PI3K/AKT and NF-κB signalling pathway genes. These findings have important implications for the diagnosis and treatment of BCA and BCAC, which, despite histopathologic overlap, may be unrelated entities.
Item Description:Gesehen am 03.11.2025
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-025-59871-3

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