Overall genomic pattern is a predictor of outcome in neuroblastoma
| Autor: | Jérôme Couturier, Dominique Plantaz, Alexander Valent, Agnès Ribeiro, Dominique Valteau-Couanet, Michel Peuchmaur, Caroline Thomas, Evi Michels, Véronique Mosseri, Isabelle Janoueix-Lerosey, Jean Michon, Delphine Lequin, Gudrun Schleiermacher, Hervé Rubie, Olivier Delattre, Angelika Eggert, Raphael Rousseau, Frank Speleman, Joëlle Vermeulen, Valérie Combaret |
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| Přispěvatelé: | Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département de Pédiatrie, INSTITUT CURIE, Center for Medical Genetics [Ghent], Ghent University Hospital, Service de biostatistique ( IC10213 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, Unité de génétique somatique, Unité de Cytogénétique, Service d'anatomie et de cytologie pathologique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy ( IGR ), Service Hématologie Infantile, CHU Grenoble, Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service Hémato-Oncologie Infantile, Laboratoire d'Oncologie Moléculaire, Centre Léon Bérard [Lyon], Department of Paediatric Oncology and Haematology, University Children's Hospital of Essen, Département d'oncologie pédiatrique, Supported by grants from the Institut National de la Sante´ et de la Recherche Me´ dicale and the Ligue Nationale contre le Cancer (Equipe labellise´ e). Construction of the BAC/PAC array was supported by grants from the Carte d'Identite´ des Tumeurs/Program of the Ligue Nationale Contre le Cancer. Belgian array-CGH results were obtained by support of the Stichting tegen Kanker and Specific Targeted Research Project. E.M. is supported by the concerted research fund (GOA, No. 12051203). J.V. is supported by the Belgian Kids' Fund., Janoueix-Lerosey, Isabelle, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Service de biostatistique (IC10213), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Institut Gustave Roussy (IGR), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université Toulouse III - Paul Sabatier (UT3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Oncology
Cancer Research Pathology Genes myc Medizin MESH: Gene Amplification [ SDV.CAN ] Life Sciences [q-bio]/Cancer MESH: Proportional Hazards Models Neuroblastoma 0302 clinical medicine MESH : Tumor Markers Biological Copy-number variation MESH : Comparative Genomic Hybridization Oligonucleotide Array Sequence Analysis 0303 health sciences Comparative Genomic Hybridization MESH : Prognosis MESH: Genomic Instability MESH : Gene Amplification MESH : Infant MESH: Follow-Up Studies DNA Neoplasm Prognosis MESH: Infant MESH : Oligonucleotide Array Sequence Analysis MESH : Genes myc 030220 oncology & carcinogenesis MESH: Survival Analysis MESH : DNA Neoplasm medicine.medical_specialty Copy number analysis MESH: DNA Neoplasm [SDV.CAN]Life Sciences [q-bio]/Cancer MESH: Prognosis MESH: Multivariate Analysis Genomic Instability 03 medical and health sciences [SDV.CAN] Life Sciences [q-bio]/Cancer Internal medicine medicine Biomarkers Tumor Humans Clinical significance Survival analysis MESH: Genes myc 030304 developmental biology Proportional Hazards Models MESH: Humans business.industry Proportional hazards model MESH : Humans Gene Amplification Cancer MESH : Multivariate Analysis Infant MESH : Follow-Up Studies medicine.disease MESH : Proportional Hazards Models MESH: Neuroblastoma Survival Analysis MESH: Comparative Genomic Hybridization MESH: Oligonucleotide Array Sequence Analysis MESH: Tumor Markers Biological Multivariate Analysis MESH : Neuroblastoma MESH : Survival Analysis business MESH : Genomic Instability Comparative genomic hybridization Follow-Up Studies |
| Zdroj: | Journal of Clinical Oncology Journal of Clinical Oncology, American Society of Clinical Oncology, 2009, 27 (7), pp.1026-33. 〈10.1200/JCO.2008.16.0630〉 Journal of Clinical Oncology, 2009, 27 (7), pp.1026-33. ⟨10.1200/JCO.2008.16.0630⟩ Journal of Clinical Oncology, American Society of Clinical Oncology, 2009, 27 (7), pp.1026-33. ⟨10.1200/JCO.2008.16.0630⟩ |
| ISSN: | 0732-183X 1527-7755 |
| DOI: | 10.1200/JCO.2008.16.0630〉 |
| Popis: | Purpose For a comprehensive overview of the genetic alterations of neuroblastoma, their association and clinical significance, we conducted a whole-genome DNA copy number analysis. Patients and Methods A series of 493 neuroblastoma (NB) samples was investigated by array-based comparative genomic hybridization in two consecutive steps (224, then 269 patients). Results Genomic analysis identified several types of profiles. Tumors presenting exclusively whole-chromosome copy number variations were associated with excellent survival. No disease-related death was observed in this group. In contrast, tumors with any type of segmental chromosome alterations characterized patients with a high risk of relapse. Patients with both numerical and segmental abnormalities clearly shared the higher risk of relapse of segmental-only patients. In a multivariate analysis, taking into account the genomic profile, but also previously described individual genetic and clinical markers with prognostic significance, the presence of segmental alterations with (HR, 7.3; 95% CI, 3.7 to 14.5; P < .001) or without MYCN amplification (HR, 4.5; 95% CI, 2.4 to 8.4; P < .001) was the strongest predictor of relapse; the other significant variables were age older than 18 months (HR, 1.8; 95% CI, 1.2 to 2.8; P = .004) and stage 4 (HR, 1.8; 95% CI, 1.2 to 2.7; P = .005). Finally, within tumors showing segmental alterations, stage 4, age, MYCN amplification, 1p and 11q deletions, and 1q gain were independent predictors of decreased overall survival. Conclusion The analysis of the overall genomic pattern, which probably unravels particular genomic instability mechanisms rather than the analysis of individual markers, is essential to predict relapse in NB patients. It adds critical prognostic information to conventional markers and should be included in future treatment stratification. |
| Databáze: | OpenAIRE |
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