DNA methylome analysis of pediatric acute lymphoblastic leukemia cells reveals stochastic de novo DNA methylation in CpG islands.

We used whole genome bisulfite sequencing (WGBS) to determine the DNA methylation levels at single base-pair resolution of four patients with different subtypes of pediatric ALL together with RNA-sequencing to increase our understanding of the leukemic transformation in ALL. The ALL genomes of four patients (Patients P1-P4) were sequenced in bone marrow samples collected at diagnosis, to an average 20-30-fold sequence depth per base. Patient 1 has the recurrent B-cell precursor ALL (BCP-ALL) translocation t(12;21)ETV6-RUNX1, Patient 2 has BCP-ALL with two non-recurrent translocations, Patient 3 has BCP-ALL with a normal karyotype, and Patient 4 has T-cell immunophenotype ALL (T-ALL). The four ALL genomes were compared to pools of B-cells (n=7) and T-cells (n=17) from healthy blood donors and a CD34+ reference (GSM791828). We also interrogated potential effects of epigenetics on gene expression using RNA-sequencing data from three of the ALL samples (P1, P2, and P4) and B- and T-cells. 450k BeadArray data GSM1203860, GSM1203904, GSM1204111 and GSM1203962 corresponding to P1-4 was used for validation. ---------------------------------------- Submitter declares reads will be made available through dbGaP/EGA