Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Apr 7;139(5):1270-1280.
doi: 10.3171/2023.1.JNS222180. Print 2023 Nov 1.

The mutational landscape of skull base and spinal chordomas and the identification of potential prognostic and theranostic biomarkers

Thibault Passeri  1   2   3 , Tom Gutman  4 , Abderaouf Hamza  1 , Homa Adle-Biassette  5 , Elodie Girard  4 , Romane Beaurepere  1 , Zakia Tariq  1 , Odette Mariani  6 , Ahmed Dahmani  3 , Christine Bourneix  1 , Rosaria Abbritti  2 , Keltouma Driouch  1 , Mylène Bohec  7 , Nicolas Servant  4 , Sylvain Baulande  7 , Didier Decaudin  3 , Jean-Pierre Guichard  8 , Valentin Calugaru  9 , Loïc Feuvret  10 , Jean-Marc Guinebretière  11 , Laurence Champion  12 , Ivan Bièche  1 , Sébastien Froelich  2 , Hamid Mammar  9 , Julien Masliah-Planchon  1
Affiliations

The mutational landscape of skull base and spinal chordomas and the identification of potential prognostic and theranostic biomarkers

Thibault Passeri et al. J Neurosurg. .

Abstract

Objective: Chordomas are rare bone neoplasms characterized by a high recurrence rate and no benefit from any approved medical treatment to date. 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: The authors conducted whole-exome sequencing (WES), targeted next-generation sequencing, and RNA sequencing of 64 skull base and spinal chordoma samples collected between December 2006 and September 2020. Clinical, histological, and radiological data were retrospectively analyzed and correlated to genetic findings.

Results: The authors identified homozygous deletions of CDKN2A/2B, PIK3CA mutations, and alterations affecting genes of SWI/SNF chromatin remodeling complexes (PBRM1 and ARID1A) as potential theranostic biomarkers. Using matched germline WES, they observed a higher frequency of a common genetic variant (rs2305089; p.(Gly177Asp)) in TBXT (97.8%, p < 0.001) compared to its distribution in the general 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 recurrent tumors.

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

Keywords: chordoma; next-generation sequencing; oncology; prognosis; skull base; theranostic biomarkers; tumor.

PubMed Disclaimer

Publication types

Substances

LinkOut - more resources