Distinction of acute lymphoblastic leukemia from acute myeloid leukemia through microarray-based DNA methylation analysis.
Patterns of DNA methylation are substantially altered in malignancies compared to normal tissue, with both genome-wide hypomethylation and regional increase of cytosine methylation at dinucleotides of cytosine and guanine, i.e., CpG dinucleotides. While genome-wide hypomethylation renders chromosomes instable, hypermethylation of CpGs in promoter regions is generally associated with transcriptional silencing, e.g., of tumor suppressor genes. To investigate whether disease-specific methylation profiles exist for different entities of acute leukemia, a microarray-based DNA methylation analysis simultaneously assessing 249 CpG dinucleotides originating from 57 genes was employed. Hereby, samples from precursor B-cell acute lymphoblastic leukemia (ALL) could be distinguished from cases of acute myeloid leukemia by virtue of N33, EGR4, CDC2, CCND2, or MOS hypermethylation in ALL.
Scholz
Christian
C
Department of Hematology and Oncology, Universitätsmedizin Berlin, Charité Campus Virchow-Klinikum, Berlin, Germany. christian.scholz@charite.de
Nimmrich
Inko
I
Burger
Matthias
M
Becker
Evelyne
E
Dörken
Bernd
B
Ludwig
Wolf-Dieter
WD
Maier
Sabine
S
D000208:Acute Disease; D001483:Base Sequence; D002965:Classification; D019175:DNA Methylation; D003937:Diagnosis, Differential; D015226:Dinucleoside Phosphates / Q000378:metabolism; D006801:Humans; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics*; D011401:Promoter Regions, Genetic
D015226:Dinucleoside Phosphates; D009363:Neoplasm Proteins; C015772:CpG dinucleotide