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Validated prediction of clinical outcome in sarcomas and multiple types of cancer on the basis of a gene expression signature related to genome complexity

Frédéric Chibon 1, 2 Pauline Lagarde 2, 1 Sebastien Salas 3 Gaëlle Pérot 2 Véronique Brouste 2 Franck Tirode 4 Carlo Lucchesi 5 Aurélien de Reyniès 6 Audrey Kauffmann 1 Binh Bui 7 Philippe Terrier 8 Sylvie Bonvalot 9 Axel Le Cesne 10 Dominique Vince-Ranchère 11 Jean-Yves Blay 11 Françoise Collin 12 Louis Guillou 13 Agnès Leroux 14 Jean-Michel Coindre 15 Alain Aurias 5
1 VINCO - Validation et identification de nouvelles cibles en oncologie
2 Institut Bergonié [Bordeaux]
3 Medical Oncology Unit
4 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
5 U830 - Unité de génétique et biologie des cancers
6 CIT - (le programme) Cartes d'identité des tumeurs
7 Département d'oncologie médicale
8 Département de biologie et pathologie médicales [Gustave Roussy]
9 CIC 1428 , CBT 507 - Centre d'Investigation Clinique en Biotherapie des cancers
10 Département de médecine oncologique [Gustave Roussy]
11 Centre Léon Bérard [Lyon]
12 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
13 Oncology - Pathology - Anatomy
14 CAV - Centre Alexis Vautrin
15 Service de Pathologie
Abstract : Sarcomas are heterogeneous and aggressive mesenchymal tumors. Histological grading has so far been the best predictor for metastasis-free survival, but it has several limitations, such as moderate reproducibility and poor prognostic value for some histological types. To improve patient grading, we performed genomic and expression profiling in a training set of 183 sarcomas and established a prognostic gene expression signature, complexity index in sarcomas (CINSARC), composed of 67 genes related to mitosis and chromosome management. In a multivariate analysis, CINSARC predicts metastasis outcome in the training set and in an independent 127 sarcomas validation set. It is superior to the Fédération Francaise des Centres de Lutte Contre le Cancer grading system in determining metastatic outcome for sarcoma patients. Furthermore, it also predicts outcome for gastrointestinal stromal tumors (GISTs), breast carcinomas and lymphomas. Application of the signature will permit more selective use of adjuvant therapies for people with sarcomas, leading to decreased iatrogenic morbidity and improved outcomes for such individuals.
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https://www.hal.inserm.fr/inserm-02438669
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Submitted on : Tuesday, January 14, 2020 - 12:14:58 PM
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INSERM | CGFL | BERGONIE | CURIE | FNCLCC | UNIV-LYON1 | UNIV-PARIS5 | CRCL | USPC | CNRS | UDL | IGR | VAUTRIN | UNIV-PARIS | PSL

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Frédéric Chibon, Pauline Lagarde, Sebastien Salas, Gaëlle Pérot, Véronique Brouste, et al.. Validated prediction of clinical outcome in sarcomas and multiple types of cancer on the basis of a gene expression signature related to genome complexity. Nature Medicine, Nature Publishing Group, 2010, 16 (7), pp.781-787. ⟨10.1038/nm.2174⟩. ⟨inserm-02438669⟩

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