DNA methylation fingerprint of neuroblastoma reveals new biological and clinical insights

• Published in: Epigenomics Vol. 7; no. 7; pp. 1137 - 1153
• Main Authors: Gómez, Soledad, Castellano, Giancarlo, Mayol, Gemma, Suñol, Mariona, Queiros, Ana, Bibikova, Marina, Nazor, Kristopher L, Loring, Jeanne F, Lemos, Isadora, Rodríguez, Eva, de Torres, Carmen, Mora, Jaume, Martín-Subero, José I, Lavarino, Cinzia
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.10.2015
• Subjects: Adrenal glands; Annotations; Brain Neoplasms - diagnosis; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - mortality; Cell Line, Tumor; Child; Child, Preschool; Chromatin; Chromatin - chemistry; Chromatin - metabolism; Cluster analysis; CpG Islands; Cyclin D1 - genetics; Cyclin D1 - metabolism; Cytosine; Deoxyribonucleic acid; development; DNA; DNA Fingerprinting; DNA Methylation; DNA methylome; DNA microarrays; DNA, Intergenic; Domains; Epigenesis, Genetic; Female; Fingerprints; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes; Genome, Human; Genomes; Guanine; Humans; Infant; Kinases; Male; Mutation; Neuroblastoma; Neuroblastoma - diagnosis; Neuroblastoma - genetics; Neuroblastoma - metabolism; Neuroblastoma - mortality; non-CpG sites; nonpromoter methylation; Oligonucleotide Array Sequence Analysis; Pathogenesis; Prognosis; Promoter Regions, Genetic; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - metabolism; Stem cells; Survival Analysis; Transcription; Tumors; ALK; DNA methylome; development; CCND1; nonpromoter methylation; neuroblastoma; non-CpG sites
• ISSN: 1750-1911; 1750-192X
• DOI: 10.2217/epi.15.49

To define the DNA methylation landscape of neuroblastoma and its clinicopathological impact. Microarray DNA methylation data were analyzed and associated with functional/regulatory genome annotation data, transcriptional profiles and clinicobiological parameters. 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 . 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 . This epigenetic fingerprint of neuroblastoma provides new insights into the pathogenesis and clinical behavior of this pediatric tumor.