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Int J Clin Exp Pathol 2010;3(3):265-279
Original Article
Molecular detection of B-cell neoplasms by specific DNA methylation biomarkers
Michael X. Wang, Huan-You Wang, Xiaohui Zhao, Nalluri Srilathaa, Huidong Shia, Jie Ninga, Deiter J. Duff, Kristen H Taylor, Barbara A Gruner,
Charles W Caldwell
Departments of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO, USA; Department of Pathology
School of Medicine, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA, USA; Department of Pathology School of
Medicine, University of California at Irvine, Orange, CA, USA; Molecular Oncology Program, Medical College of Georgia Cancer Center, Augusta,
GA, USA; Children’s Hospital, Columbia, University of Missouri Health Care, Columbia, MO, USA
Received December 15, 2009; accepted January 26, 2010; available online: January 28, 2010.
Abstract: 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 BALL 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 has potential use in both the diagnosis of B-cell neoplasia and detection of minimal
residual disease, in addition to classical approach of clinical features, morphology, immunophenotype, and genetic analysis. (IJCEP912004).
Key words: Mature B-cell neoplasms, B lymphoblastic leukemia, DNA methylation biomarker, minimal residual disease
Full text PDF
Address all correspondence to:
Michael X. Wang, M.D., Ph.D.
Department of Pathology and Anatomical Sciences
Ellis Fischel Cancer Center
University of Missouri Health Science Center
115 Business Loop 70 West
Columbia, MO 65203
Tel: (573) 882-1276
Fax: (573) 884-5206
E-mail: wangmx@health.missouri.edu
Original Article
Molecular detection of B-cell neoplasms by specific DNA methylation biomarkers
Michael X. Wang, Huan-You Wang, Xiaohui Zhao, Nalluri Srilathaa, Huidong Shia, Jie Ninga, Deiter J. Duff, Kristen H Taylor, Barbara A Gruner,
Charles W Caldwell
Departments of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO, USA; Department of Pathology
School of Medicine, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA, USA; Department of Pathology School of
Medicine, University of California at Irvine, Orange, CA, USA; Molecular Oncology Program, Medical College of Georgia Cancer Center, Augusta,
GA, USA; Children’s Hospital, Columbia, University of Missouri Health Care, Columbia, MO, USA
Received December 15, 2009; accepted January 26, 2010; available online: January 28, 2010.
Abstract: 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 BALL 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 has potential use in both the diagnosis of B-cell neoplasia and detection of minimal
residual disease, in addition to classical approach of clinical features, morphology, immunophenotype, and genetic analysis. (IJCEP912004).
Key words: Mature B-cell neoplasms, B lymphoblastic leukemia, DNA methylation biomarker, minimal residual disease
Full text PDF
Address all correspondence to:
Michael X. Wang, M.D., Ph.D.
Department of Pathology and Anatomical Sciences
Ellis Fischel Cancer Center
University of Missouri Health Science Center
115 Business Loop 70 West
Columbia, MO 65203
Tel: (573) 882-1276
Fax: (573) 884-5206
E-mail: wangmx@health.missouri.edu
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