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.
Wang
Michael X
MX
Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO, USA. wangmx@health.missouri.edu
Wang
Huan-You
HY
Zhao
Xiaohui
X
Srilatha
Nalluri
N
Zheng
Dali
D
Shi
Huidong
H
Ning
Jie
J
Duff
Deiter J
DJ
Taylor
Kristen H
KH
Gruner
Barbara A
BA
Caldwell
Charles W
CW
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