Abstract
Aim: To determine whether methylation differences between mostly fatal TCF3-HLF and curable TCF3-PBX1 pediatric acute lymphoblastic leukemia subtypes can be associated with differential gene expression and remission. Materials & methods: Five (extremely rare) TCF3-HLF versus five (very similar) TCF3-PBX1 patients were sampled before and after remission and analyzed using reduced representation bisulfite sequencing and RNA-sequencing. Results: We identified 7000 differentially methylated CpG sites between subtypes, of which 78% had lower methylation levels in TCF3-HLF. Gene expression was negatively correlated with CpG sites in 23 genes. KBTBD11 clearly differed in methylation and expression between subtypes and before and after remission in TCF3-HLF samples. Conclusion: KBTBD11 hypomethylation may be a promising potential target for further experimental validation especially for the TCF3-HLF subtype.
| Original language | English |
|---|---|
| Journal | Epigenomics |
| Volume | 10 |
| Issue number | 2 |
| Pages (from-to) | 133-147 |
| Number of pages | 15 |
| ISSN | 1750-1911 |
| DOIs | |
| Publication status | Published - 02.2018 |
Funding
This study was carried out as part of the Research Training Group ‘Genes, Environment and Inflammation,’ supported by the Deutsche Forschungsgemeinschaft (GRK 1743). This work was supported by the German Federal Office for Radiation Protection (Grant no. St.Sch. 3611S70014), by the Swiss National Research Foundation SNF 310030–133108, the foundation ‘Kind und Krebs,’ the ‘Krebsliga Zurich,’ the Sassella Foundation, the Fondation Panacée, the clinical research focus program ‘Human Hemato-Lymphatic Diseases’ of the University of Zurich, the ‘Deutsche Forschungsgemeinschaft’ (DFG), Clusters of Excellence ‘Inflammation at Interfaces,’ the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (grant number 01ZX1306A, sysINFLAME), the EU Seventh Framework Program [FP7/2007–2013, Grant no. 262055, ESGI; FP7-HEALTH-F2–2011 Grant no. 261474, ENCCA; ERA-Net Transcan, Validation of biomarkers for personalized cancer medicine, TRANSCALL; Health-F2–2010 Grant no. 260791, EUROCANPLATFORM], the ‘Katharina Hardt Stiftung,’ the ‘Deutsche José Carreras Leukämie-Stiftung,’ the ‘Madeleine Schickedanz-Kinderkrebs-Stiftung,’ the ‘Deutsche Krebshilfe – Dr. Mildred Scheel Stiftung (Grant no. 108613),’ the Foundation of Experimental Biomedicine in Zurich, the Max Planck Society and the ‘Elternverein zur Förderung der Behandlung krebskranker Kinder Hannover e.V.’ The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
