Molecular detection of B-cell neoplasms by specific DNA methylation biomarkers.
A novel, easy to perform PCR-based method employing specific DNA methylation biomarkers to detect B-cell neoplasms in a variety of B-cell lines and B lymphoblastic leukemia (B-ALL) patient specimens has been developed. This method detects as few as 5 B-ALL cells, or 1 B-ALL cell in 1,000,000 normal background blood cells using a single marker, DLC-1 gene CpG island (CGI) methylation. By adding two additional markers PCDHGA12 and RPIB9, over 80% of B-ALL cases were detected in patients' bone marrow and/or peripheral blood specimens. We have traced clinical B-ALL cases up to 10 years retrospectively and the DLC-1 methylation is correlated with patient clinical status. Thus, this epigenetic-based molecular method demonstrates its potential use in the diagnosis of B-cell neoplasia, in addition to traditional approach such as clinical features, morphology, immunophenotype, and genetic analysis.
Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO, USA. wangmx@health.missouri.edu
Michael X
MX
Wang
Huan-You
HY
Wang
Xiaohui
X
Zhao
Nalluri
N
Srilatha
Dali
D
Zheng
Huidong
H
Shi
Jie
J
Ning
Deiter J
DJ
Duff
Kristen H
KH
Taylor
Barbara A
BA
Gruner
Charles W
CW
Caldwell
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D020690:GTPase-Activating Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015448:Leukemia, B-Cell / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C112352:DLC1 protein, human; D004273:DNA, Neoplasm; D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C477805:RUNDC3B protein, human; D025521:Tumor Suppressor Proteins
B lymphoblastic leukemia; DNA methylation biomarker; Mature B-cell neoplasms