title: Genomic Copy Number Profiling Using Circulating Free Tumor DNA Highlights Heterogeneity in Neuroblastoma.
abstract: OBJECTIVE
  The tumor genomic copy number profile is of prognostic significance in neuroblastoma patients. We have studied the genomic copy number profile of cell-free DNA (cfDNA) and compared this with primary tumor arrayCGH (aCGH) at diagnosis.
  
  
  METHODS
  In 70 patients, cfDNA genomic copy number profiling was performed using the OncoScan platform. The profiles were classified according to the overall pattern, including numerical chromosome alterations (NCA), segmental chromosome alterations (SCA), and MYCN amplification (MNA).
  
  
  RESULTS
  Interpretable and dynamic cfDNA profiles were obtained in 66 of 70 and 52 of 70 cases, respectively. An overall identical genomic profile between tumor aCGH and cfDNA was observed in 47 cases (3 NCAs, 22 SCAs, 22 MNAs). In one case, cfDNA showed an additional SCA not detected by tumor aCGH. In 4 of 8 cases with a silent tumor aCGH profile, cfDNA analysis revealed a dynamic profile (3 SCAs, 1 NCA). In 14 cases, cfDNA analysis did not reveal any copy number changes. A total of 378 breakpoints common to the primary tumor and cfDNA of any given patient were identified, 27 breakpoints were seen by tumor aCGH, and 54 breakpoints were seen in cfDNA only, including two cases with interstitial IGFR1 gains and two alterations targeting TERT CONCLUSIONS: These results demonstrate the feasibility of cfDNA copy number profiling in neuroblastoma patients, with a concordance of the overall genomic profile in aCGH and cfDNA dynamic cases of 97% and a sensitivity of 77%, respectively. Furthermore, neuroblastoma heterogeneity is highlighted, suggesting that cfDNA might reflect genetic alterations of more aggressive cell clones. Clin Cancer Res; 22(22); 5564-73. ©2016 AACRSee related commentary by Janku and Kurzrock, p. 5400.
authors.affiliation: INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Research Center, Institut Curie, Paris Sciences et Lettres Research University, Paris, France.|Translational Research Department, SiRIC RTOP Recherche Translationelle en Oncologie Pédiatrique, Research Center, Institut Curie, Paris Sciences et Lettres Research University, Paris, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Chicard
authors.affiliation: Plateforme de Génomique des Cancers, Centre Léon Bérard, Lyon, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Boyault
authors.affiliation: INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Research Center, Institut Curie, Paris Sciences et Lettres Research University, Paris, France.|Translational Research Department, SiRIC RTOP Recherche Translationelle en Oncologie Pédiatrique, Research Center, Institut Curie, Paris Sciences et Lettres Research University, Paris, France.
authors.forename: Leo
authors.initials: L
authors.lastname: Colmet Daage
authors.affiliation: INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Research Center, Institut Curie, Paris Sciences et Lettres Research University, Paris, France.|Translational Research Department, SiRIC RTOP Recherche Translationelle en Oncologie Pédiatrique, Research Center, Institut Curie, Paris Sciences et Lettres Research University, Paris, France.
authors.forename: Wilfrid
authors.initials: W
authors.lastname: Richer
authors.affiliation: Translational Research Department, Genomic Platform, Research Center, Institut Curie, Paris Sciences et Lettres Research University, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Gentien
authors.affiliation: Unité de Génétique Somatique, Service de Génétique, Hospital Group, Institut Curie, Paris, France.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Pierron
authors.affiliation: Unité de Génétique Somatique, Service de Génétique, Hospital Group, Institut Curie, Paris, France.
authors.forename: Eve
authors.initials: E
authors.lastname: Lapouble
authors.affiliation: INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Research Center, Institut Curie, Paris Sciences et Lettres Research University, Paris, France.|Translational Research Department, SiRIC RTOP Recherche Translationelle en Oncologie Pédiatrique, Research Center, Institut Curie, Paris Sciences et Lettres Research University, Paris, France.
authors.forename: Angela
authors.initials: A
authors.lastname: Bellini
authors.affiliation: INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Research Center, Institut Curie, Paris Sciences et Lettres Research University, Paris, France.|Department of Pediatric Oncology, Hospital Group, Institut Curie, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Clement
authors.affiliation: Laboratoire de Recherche Translationnelle, Centre Léon-Bérard, Lyon, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Iacono
authors.affiliation: Laboratoire de Recherche Translationnelle, Centre Léon-Bérard, Lyon, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bréjon
authors.affiliation: Plateforme de Génomique des Cancers, Centre Léon Bérard, Lyon, France.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Carrere
authors.affiliation: Translational Research Department, Genomic Platform, Research Center, Institut Curie, Paris Sciences et Lettres Research University, Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Reyes
authors.affiliation: INSERM U900, Bioinformatics, Biostatistics, Epidemiology and Computational Systems Biology of Cancer, Research Center, Institut Curie, Paris Sciences et Lettres Research University, Paris, France.
authors.forename: Toby
authors.initials: T
authors.lastname: Hocking
authors.affiliation: Institut Curie Genomics of Excellence (ICGex) Platform, Research Center, Institut Curie, Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Bernard
authors.affiliation: Service de Pathologie, Hôpital Robert Debré, APHP and Université Paris Diderot Paris 7, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Peuchmaur
authors.affiliation: Institut d'Hematologie et d'Oncologie Pédiatrique, Centre Léon Bérard, Lyon, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Corradini
authors.affiliation: Institut d'Hematologie et d'Oncologie Pédiatrique, Centre Léon Bérard, Lyon, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Faure-Conter
authors.affiliation: Service d'Oncologie Pédiatrique, Hôpital de la Timone, CHU de Marseille, Marseille, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Coze
authors.affiliation: Service d'Hémato-Oncologie Pédiatrique, CHU Grenoble, Grenoble, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Plantaz
authors.affiliation: Service d'Oncologie Pédiatrique, Centre Oscar Lambret, Lille, France.
authors.forename: Anne Sophie
authors.initials: AS
authors.lastname: Defachelles
authors.affiliation: Service d'Hémato-Oncologie Pédiatrique, CHU Nantes, Nantes, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Thebaud
authors.affiliation: Unite d'Hemato-Oncologie, Hôpital des Enfants, Toulouse, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Gambart
authors.affiliation: Unité d'onco-hématologie pédiatrique, CHU de Poitiers, Poitiers, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Millot
authors.affiliation: Department of Pediatric Oncology, Institut Gustave Roussy, Villejuif, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Valteau-Couanet
authors.affiliation: Department of Pediatric Oncology, Hospital Group, Institut Curie, Paris, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Michon
authors.affiliation: INSERM UMR-S1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Puisieux
authors.affiliation: INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Research Center, Institut Curie, Paris Sciences et Lettres Research University, Paris, France.|Translational Research Department, SiRIC RTOP Recherche Translationelle en Oncologie Pédiatrique, Research Center, Institut Curie, Paris Sciences et Lettres Research University, Paris, France.|Unité de Génétique Somatique, Service de Génétique, Hospital Group, Institut Curie, Paris, France.|Institut Curie Genomics of Excellence (ICGex) Platform, Research Center, Institut Curie, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
authors.affiliation: Laboratoire de Recherche Translationnelle, Centre Léon-Bérard, Lyon, France. gudrun.schleiermacher@curie.fr valerie.combaret@lyon.unicancer.fr.
authors.forename: Valérie
authors.initials: V
authors.lastname: Combaret
authors.affiliation: INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Research Center, Institut Curie, Paris Sciences et Lettres Research University, Paris, France. gudrun.schleiermacher@curie.fr valerie.combaret@lyon.unicancer.fr.|Translational Research Department, SiRIC RTOP Recherche Translationelle en Oncologie Pédiatrique, Research Center, Institut Curie, Paris Sciences et Lettres Research University, Paris, France.|Department of Pediatric Oncology, Hospital Group, Institut Curie, Paris, France.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Schleiermacher
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D000074141:Circulating Tumor DNA / Q000235:genetics*; D055028:Comparative Genomic Hybridization / Q000379:methods; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D018628:Gene Dosage / Q000235:genetics*; D023281:Genomics / Q000379:methods; D006801:Humans; D007223:Infant; D008297:Male; D009447:Neuroblastoma / Q000097:blood* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D000074141:Circulating Tumor DNA