IgH gene rearrangements as plasma biomarkers in Non-Hodgkin's Lymphoma patients

Jian He; Jian Wu; Yuchen Jiao; Nina Wagner-Johnston; Richard F. Ambinder; Luis A. Diaz; Kenneth W. Kinzler; Bert Vogelstein; Nickolas Papadopoulos

doi:10.18632/oncotarget.235

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Research Papers:

IgH gene rearrangements as plasma biomarkers in Non-Hodgkin's Lymphoma patients

Jian He, Jian Wu, Yuchen Jiao, Nina Wagner-Johnston, Richard F. Ambinder, Luis A. Diaz, Kenneth W. Kinzler, Bert Vogelstein _ and Nickolas Papadopoulos

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Oncotarget. 2011; 2:178-185. https://doi.org/10.18632/oncotarget.235

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Abstract

Jian He^1*, Jian Wu^1*, Yuchen Jiao¹, Nina Wagner-Johnston², Richard F. Ambinder³, Luis A Diaz Jr¹, Kenneth W Kinzler¹, Bert Vogelstein¹, and Nickolas Papadopoulos¹

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;

Correspondence:

Bert Vogelstein, e-mail:

Abstract

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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Research Papers:

IgH gene rearrangements as plasma biomarkers in Non-Hodgkin's Lymphoma patients

Abstract