DNA methylation-based subtype prediction for pediatric acute lymphoblastic leukemia

Clinical Epigenetics
Jessica NordlundAnn-Christine Syvänen

Abstract

We present a method that utilizes DNA methylation profiling for prediction of the cytogenetic subtypes of acute lymphoblastic leukemia (ALL) cells from pediatric ALL patients. The primary aim of our study was to improve risk stratification of ALL patients into treatment groups using DNA methylation as a complement to current diagnostic methods. A secondary aim was to gain insight into the functional role of DNA methylation in ALL. We used the methylation status of ~450,000 CpG sites in 546 well-characterized patients with T-ALL or seven recurrent B-cell precursor ALL subtypes to design and validate sensitive and accurate DNA methylation classifiers. After repeated cross-validation, a final classifier was derived that consisted of only 246 CpG sites. The mean sensitivity and specificity of the classifier across the known subtypes was 0.90 and 0.99, respectively. We then used DNA methylation classification to screen for subtype membership of 210 patients with undefined karyotype (normal or no result) or non-recurrent cytogenetic aberrations ('other' subtype). Nearly half (n = 106) of the patients lacking cytogenetic subgrouping displayed highly similar methylation profiles as the patients in the known recurrent groups. We verifie...Continue Reading

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Datasets Mentioned

BETA
GSE49031

Methods Mentioned

BETA
PCR
methylation profiling
chromosomal aberration
chromosomal aberrations
RNA-seq
genotyping

Software Mentioned

FusionCatcher
EsPhALL
integrative genomics viewer ( IGV )
NOPHO
R
preprocessCore

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