J Neurol Surg B Skull Base 2023; 84(S 01): S1-S344
DOI: 10.1055/s-0043-1762203
Presentation Abstracts
Oral Abstracts

The Mutational Landscape of Skull-Base and Spinal Chordomas Identifies Potential Prognostic and Theranostic Biomarkers

Thibault Passeri
1   Department of Neurosurgery, Lariboisière Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France
,
Tom Gutman
2   Inserm U900, Institut Curie, Paris, France
,
Abderaouf Hamza
3   Department of Genetics, Institut Curie, Paris, France
,
Homa Adle-Biassette
4   Department of Pathology, Lariboisière Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France
,
Elodie Girard
2   Inserm U900, Institut Curie, Paris, France
,
Romane Beaurepere
3   Department of Genetics, Institut Curie, Paris, France
,
Zakia Tariq
3   Department of Genetics, Institut Curie, Paris, France
,
Odette Mariani
5   Department of Tumor Biology, Institut Curie, Paris, France
,
Ahmed Dahmani
6   Laboratory of Preclinical Investigation, Translational Research Department, Paris-Saclay University, Institut Curie, Paris, France
,
Christine Bourneix
3   Department of Genetics, Institut Curie, Paris, France
,
Rosaria Abbritti
1   Department of Neurosurgery, Lariboisière Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France
,
Keltouma Driouch
3   Department of Genetics, Institut Curie, Paris, France
,
Mylène Bohec
7   ICGex NGS Platform, Institut Curie, Paris, France
,
Nicolas Servant
2   Inserm U900, Institut Curie, Paris, France
,
Sylvain Baulande
7   ICGex NGS Platform, Institut Curie, Paris, France
,
Didier Decaudin
6   Laboratory of Preclinical Investigation, Translational Research Department, Paris-Saclay University, Institut Curie, Paris, France
,
Marc Polivka
4   Department of Pathology, Lariboisière Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France
,
Jean-Pierre Guichard
8   Department of Neuroradiology, Lariboisière Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France
,
Valentin Calugaru
9   Proton Beam Therapy, Institut Curie, Paris, France
,
Loic Feuvret
9   Proton Beam Therapy, Institut Curie, Paris, France
,
Jean-Marc Guinebretière
5   Department of Tumor Biology, Institut Curie, Paris, France
,
Laurence Champion
10   Department of Nuclear Medicine, Institut Curie, Paris-Saclay University, Saint-Cloud, Paris, France
,
Ivan Bièche
3   Department of Genetics, Institut Curie, Paris, France
,
Sébastien Froelich
1   Department of Neurosurgery, Lariboisière Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France
,
Hamid Mammar
9   Proton Beam Therapy, Institut Curie, Paris, France
,
Julien Masliah-Planchon
3   Department of Genetics, Institut Curie, Paris, France
› Author Affiliations
› Further Information
Also available at
 
 

    Background: Chordomas are rare bone neoplasms characterized by a high recurrence rate and not benefitting from, to date, any approved medical treatment. However, the investigation of molecular alterations in chordomas could be essential to prognosticate, guide clinical decision-making and identify theranostic biomarkers. The aim of this study was to provide a detailed genomic landscape of a homogeneous series of 64 chordoma samples, revealing driver events, theranostic markers, and outcome-related genomic features.

    Methods: We conducted whole-exome sequencing (WES), targeted-NGS and RNAseq of 64 skull base and spinal chordomas. Clinical, histological, and radiological data were retrospectively analyzed and correlated to genetic findings.

    Results: We identified homozygous deletions of the CDKN2A/2B genes, PIK3CA mutations, and alterations affecting genes of SWI/SNF chromatin remodeling complexes (PBRM1 and ARID1A) as potential theranostic biomarkers. Using matched germline WES, we observed a higher frequency of a common genetic variant (rs2305089; p.(Gly177Asp)) in the TBXTgene (98.7%, p < 0.001) compared with its distribution in the population. PIK3CA mutation was identified as an independent biomarker of short progression-free survival (HR = 10.68, p = 0.0008). Loss of CDKN2A/2B was more frequently observed in spinal tumors, and in recurrent tumors.

    Conclusion: In our current study, we identified driver events such as PBRM1, PIK3CA mutations, TBXT alterations or homozygous deletion of CDKN2A/2B, which could, for some, be considered potential theranostic markers and allow identifying novel therapeutic approaches. In the aim of a future biomolecular prognostication classification, alterations affecting the PIK3CA and CDKN2A/2B could be considered as poor prognostic biomarkers.

    Zoom Image
    Zoom Image

    #

    No conflict of interest has been declared by the author(s).

    Publication History

    Article published online:
    01 February 2023

    © 2023. Thieme. All rights reserved.

    Georg Thieme Verlag KG
    Rüdigerstraße 14, 70469 Stuttgart, Germany

     
    Zoom Image
    Zoom Image