title: DNA methylation fingerprint of neuroblastoma reveals new biological and clinical insights.
abstract: OBJECTIVE
  To define the DNA methylation landscape of neuroblastoma and its clinicopathological impact.
  
  
  METHODS
  Microarray DNA methylation data were analyzed and associated with functional/regulatory genome annotation data, transcriptional profiles and clinicobiological parameters.
  
  
  RESULTS
  DNA methylation changes in neuroblastoma affect not only promoters but also intragenic and intergenic regions at cytosine-phosphate-guanine (CpG) and non-CpG sites, and target functional chromatin domains of development and cancer-related genes such as CCND1. Tumors with diverse clinical risk showed differences affecting CpG and, remarkably, non-CpG sites. Non-CpG methylation observed essentially in clinically favorable cases was associated with the differentiation status of neuroblastoma and expression of key genes such as ALK.
  
  
  CONCLUSIONS
  This epigenetic fingerprint of neuroblastoma provides new insights into the pathogenesis and clinical behavior of this pediatric tumor.
authors.affiliation: Developmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Edificio Docente 4th floor, C/Santa Rosa 39-57, 08950 Esplugues de Llobregat, Barcelona, Spain.
authors.forename: Soledad
authors.initials: S
authors.lastname: Gómez
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, 08036, Spain.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Castellano
authors.affiliation: Developmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Edificio Docente 4th floor, C/Santa Rosa 39-57, 08950 Esplugues de Llobregat, Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Mayol
authors.affiliation: Department of Pathology, Hospital Sant Joan de Déu, Barcelona, 08950, Spain.
authors.forename: Mariona
authors.initials: M
authors.lastname: Suñol
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, 08036, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Queiros
authors.affiliation: Illumina, Inc., San Diego, CA 92122, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Bibikova
authors.affiliation: Center for Regenerative Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Kristopher L
authors.initials: KL
authors.lastname: Nazor
authors.affiliation: Center for Regenerative Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jeanne F
authors.initials: JF
authors.lastname: Loring
authors.affiliation: Developmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Edificio Docente 4th floor, C/Santa Rosa 39-57, 08950 Esplugues de Llobregat, Barcelona, Spain.
authors.forename: Isadora
authors.initials: I
authors.lastname: Lemos
authors.affiliation: Developmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Edificio Docente 4th floor, C/Santa Rosa 39-57, 08950 Esplugues de Llobregat, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Rodríguez
authors.affiliation: Developmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Edificio Docente 4th floor, C/Santa Rosa 39-57, 08950 Esplugues de Llobregat, Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: de Torres
authors.affiliation: Developmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Edificio Docente 4th floor, C/Santa Rosa 39-57, 08950 Esplugues de Llobregat, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Mora
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, 08036, Spain.|Department of Anatomic Pathology, Pharmacology & Microbiology, University of Barcelona, Barcelona, 08036, Spain.
authors.forename: José I
authors.initials: JI
authors.lastname: Martín-Subero
authors.affiliation: Developmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Edificio Docente 4th floor, C/Santa Rosa 39-57, 08950 Esplugues de Llobregat, Barcelona, Spain.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Lavarino
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D018899:CpG Islands; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D016172:DNA Fingerprinting; D019175:DNA Methylation; D021901:DNA, Intergenic; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D007223:Infant; D008297:Male; D009447:Neuroblastoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011401:Promoter Regions, Genetic; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis
chemical_list: C530104:CCND1 protein, human; D002843:Chromatin; D021901:DNA, Intergenic; D019938:Cyclin D1; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK; CCND1; DNA methylome; development; neuroblastoma; non-CpG sites; nonpromoter methylation