Validation of DNA methylation to predict outcome in acute myeloid leukemia by use of xMELP
GBW Wertheim, C Smith, M Luskin, A Rager… - Clinical …, 2015 - academic.oup.com
Clinical chemistry, 2015•academic.oup.com
BACKGROUND Epigenetic dysregulation involving alterations in DNA methylation is a
hallmark of various types of cancer, including acute myeloid leukemia (AML). Although
specific cancer types and clinical aggressiveness of tumors can be determined by DNA
methylation status, the assessment of DNA methylation at multiple loci is not routinely
performed in the clinical laboratory. METHODS We recently described a novel microsphere-
based assay for multiplex evaluation of DNA methylation. In the current study, we validated …
hallmark of various types of cancer, including acute myeloid leukemia (AML). Although
specific cancer types and clinical aggressiveness of tumors can be determined by DNA
methylation status, the assessment of DNA methylation at multiple loci is not routinely
performed in the clinical laboratory. METHODS We recently described a novel microsphere-
based assay for multiplex evaluation of DNA methylation. In the current study, we validated …
BACKGROUND
Epigenetic dysregulation involving alterations in DNA methylation is a hallmark of various types of cancer, including acute myeloid leukemia (AML). Although specific cancer types and clinical aggressiveness of tumors can be determined by DNA methylation status, the assessment of DNA methylation at multiple loci is not routinely performed in the clinical laboratory.
METHODS
We recently described a novel microsphere-based assay for multiplex evaluation of DNA methylation. In the current study, we validated and used an improved assay [termed expedited microsphere HpaII small fragment Enrichment by Ligation-mediated PCR (xMELP)] that can be performed with appropriate clinical turnaround time.
RESULTS
Using the xMELP assay in conjunction with a new 17-locus random forest classifier that has been trained using 344 AML samples, we were able to segregate an independent cohort of 70 primary AML patients into methylation-determined subgroups with significantly distinct mortality risk (P = 0.009). We also evaluated precision, QC parameters, and preanalytic variables of the xMELP assay and determined the sensitivity of the random forest classifier score to failure at 1 or more loci.
CONCLUSIONS
Our results demonstrate that xMELP performance is suitable for implementation in the clinical laboratory and predicts AML outcome in an independent patient cohort.
Oxford University Press