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The mutational landscape of skull base and spinal chordomas and the identification of potential prognostic and theranostic biomarkers.
Passeri, Thibault; Gutman, Tom; Hamza, Abderaouf; Adle-Biassette, Homa; Girard, Elodie; Beaurepere, Romane; Tariq, Zakia; Mariani, Odette; Dahmani, Ahmed; Bourneix, Christine; Abbritti, Rosaria; Driouch, Keltouma; Bohec, Mylène; Servant, Nicolas; Baulande, Sylvain; Decaudin, Didier; Guichard, Jean-Pierre; Calugaru, Valentin; Feuvret, Loïc; Guinebretière, Jean-Marc; Champion, Laurence; Bièche, Ivan; Froelich, Sébastien; Mammar, Hamid; Masliah-Planchon, Julien.
Afiliação
  • Passeri T; Departments of1Genetics and.
  • Gutman T; Departments of2Neurosurgery.
  • Hamza A; 3Department of Translational Research, Laboratory of Preclinical Investigation, Institut Curie, Paris-Saclay University, Paris.
  • Adle-Biassette H; 4Inserm U900, Institut Curie, Paris.
  • Girard E; Departments of1Genetics and.
  • Beaurepere R; 5Pathology, and.
  • Tariq Z; 4Inserm U900, Institut Curie, Paris.
  • Mariani O; Departments of1Genetics and.
  • Dahmani A; Departments of1Genetics and.
  • Bourneix C; 6Tumor Biology, Institut Curie, Paris.
  • Abbritti R; 3Department of Translational Research, Laboratory of Preclinical Investigation, Institut Curie, Paris-Saclay University, Paris.
  • Driouch K; Departments of1Genetics and.
  • Bohec M; Departments of2Neurosurgery.
  • Servant N; Departments of1Genetics and.
  • Baulande S; 7ICGex NGS Platform, Institut Curie, Paris.
  • Decaudin D; 4Inserm U900, Institut Curie, Paris.
  • Guichard JP; 7ICGex NGS Platform, Institut Curie, Paris.
  • Calugaru V; 3Department of Translational Research, Laboratory of Preclinical Investigation, Institut Curie, Paris-Saclay University, Paris.
  • Feuvret L; 8Radiology, Lariboisière Hospital, Assistance Publique des Hôpitaux de Paris, University of Paris, Paris.
  • Guinebretière JM; 9Department of Radiotherapy, Proton Therapy Center, Institut Curie, Paris-Saclay University, Orsay.
  • Champion L; 10Department of Radiotherapy, Pitié-Salpêtrière Hospital, Assistance Publique des Hôpitaux de Paris, Paris.
  • Bièche I; 11Department of Pathology, Institut Curie, Paris-Saclay University, Paris; and.
  • Froelich S; 12Department of Nuclear Medicine, Institut Curie, Paris-Saclay University, Saint-Cloud, France.
  • Mammar H; Departments of1Genetics and.
  • Masliah-Planchon J; Departments of2Neurosurgery.
J Neurosurg ; 139(5): 1270-1280, 2023 11 01.
Article em En | MEDLINE | ID: mdl-37029667
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Coluna Vertebral / Cordoma / Neoplasias da Base do Crânio Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Coluna Vertebral / Cordoma / Neoplasias da Base do Crânio Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article