Integration of high-resolution methylome and transcriptome analyses to dissect epigenomic changes in childhood acute lymphoblastic leukemia

ABSTRACT: B-cell precursor acute lymphoblastic leukemia (pre-B ALL) is the most common pediatric cancer. Although the genetic origin of the disease remains unclear, epigenetic modifications including DNA methylation are suggested to contribute significantly to leukemogenesis. We assessed the DNA methylation status of 402,842 CpG-sites across the genome (Illumina 450k array) in tumor and remission samples of 46 pre-B ALL patients, thus generating the most comprehensive single CpG-site resolution pre-B ALL methylomes so far. Unsupervised hierarchical clustering of CpG-site neighborhood, protein-coding gene, or miRNA gene associated methylation levels separated the tumor cohort according to major pre-B ALL subtypes, and methylation in CpG islands, shores, and in regions around the transcription start site of protein-coding genes strongly correlated with transcript expression. Focusing on samples carrying the t(12;21)(p13;q22) translocation (ETV6-RUNX1 fusion gene) we identified subtype-specific methylation of 430 CpG-sites. Pathway analyses implied the associated genes in hematopoiesis and cancer. Further intersection with transcriptome data identified methylation to impact expression of 18 genes. In summary, our data illustrate the power of methylation profiling to classify leukemic subtypes and to identify subtype-specific methylation markers. Further, we demonstrate that integration of methylome and transcriptome alterations allows the study of downstream effects of individual genomic rearrangements in cancer. Bisulfite converted DNA of tumor (isolated on day of diagnosis) and remission (isolated after disease remission) samples derived from 46 patients of French-Canadian origin diagnosed with pre-B ALL were analyzed on the Illumina Infinium HumanMethylation 450k BeadChips.

ORGANISM(S): Homo sapiens

SUBMITTER: Stephan Busche 

PROVIDER: E-GEOD-38235 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress