IgH gene rearrangements as plasma biomarkers in Non-Hodgkin's Lymphoma patients
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1The Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, MD
2Washington University School of Medicine, St. Luis, MO
3The Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, MD
*J.H. and J.W. contributed equally to this work
Keywords: Cancer, leukemia, lymphoma, biomarkers, gene rearrangements
Received: March 6, 2011; Accepted: March 7, 2011; Published: March 8, 2011;
Bert Vogelstein, e-mail:
New biomarkers with improved accuracy could be helpful for monitoring disease in patients with Non-Hodgkin's lymphomas (NHL). Towards this end, we have explored the feasibility of identifying the sequence of rearranged IgH genes using next-generation sequencing, then using PCR to detect specific rearranged DNA fragments in patients’ plasma. By capturing and sequencing the IgH genomic regions (IgCap), we were able to detect and precisely determine the sequence of rearranged IgH loci in the tumors of three NHL patients. Moreover, circulating rearranged DNA fragments could be identified in the plasma of all three patients. Even in cases wherein tumor biopsies were unavailable, we were able to use the IgH capture approach to identify rearranged DNA loci in the plasma of 8 of 14 patients. IgCap may enable a more informed management of selected patients with NHL and other B-cell malignancies in the future.
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