Soledad Gómez1, Giancarlo Castellano2, Gemma Mayol1, Mariona Suñol3, Ana Queiros2, Marina Bibikova4, Kristopher L Nazor5, Jeanne F Loring5, Isadora Lemos1, Eva Rodríguez1, Carmen de Torres1, Jaume Mora1, José I Martín-Subero2,6, Cinzia Lavarino1. 1. Developmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Edificio Docente 4th floor, C/Santa Rosa 39-57, 08950 Esplugues de Llobregat, Barcelona, Spain. 2. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, 08036, Spain. 3. Department of Pathology, Hospital Sant Joan de Déu, Barcelona, 08950, Spain. 4. Illumina, Inc., San Diego, CA 92122, USA. 5. Center for Regenerative Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA. 6. Department of Anatomic Pathology, Pharmacology & Microbiology, University of Barcelona, Barcelona, 08036, Spain.
Abstract
AIM: To define the DNA methylation landscape of neuroblastoma and its clinicopathological impact. MATERIALS & 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. CONCLUSION: This epigenetic fingerprint of neuroblastoma provides new insights into the pathogenesis and clinical behavior of this pediatric tumor.
AIM: To define the DNA methylation landscape of neuroblastoma and its clinicopathological impact. MATERIALS & 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. CONCLUSION: This epigenetic fingerprint of neuroblastoma provides new insights into the pathogenesis and clinical behavior of this pediatric tumor.
Authors: Isabelle Westerlund; Yao Shi; Konstantinos Toskas; Stuart M Fell; Shuijie Li; Olga Surova; Erik Södersten; Per Kogner; Ulrika Nyman; Susanne Schlisio; Johan Holmberg Journal: Proc Natl Acad Sci U S A Date: 2017-07-10 Impact factor: 11.205