Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling

Ash A. Alizadeh, Michael B. Eisen, R. Eric Davis, Chi Ma, Izidore S. Lossos, Andreas Rosenwald, Jennifer C. Boldrick, Hajeer Sabet, Truc Tran, Xin Yu, John I. Powell, Liming Yang, Gerald E. Marti, Troy Moore, James Hudson, Lisheng Lu, David B. Lewis, Robert Tibshirani, Gavin Sherlock, Wing C. Chan, Timothy C. Greiner, Dennis D. Weisenburger, James O. Armitage, Roger Warnke, Ronald Levy, Wyndham Wilson, Michael R. Grever, John C. Byrd, David Botstein, Patrick O. Brown () and Louis M. Staudt ()
Additional contact information
Ash A. Alizadeh: Departments of Biochemistry
Michael B. Eisen: Genetics
R. Eric Davis: Metabolism Branch, National Cancer Institute, National Institutes of Health
Chi Ma: Metabolism Branch, National Cancer Institute, National Institutes of Health
Izidore S. Lossos: Medicine
Andreas Rosenwald: Metabolism Branch, National Cancer Institute, National Institutes of Health
Jennifer C. Boldrick: Departments of Biochemistry
Hajeer Sabet: Metabolism Branch, National Cancer Institute, National Institutes of Health
Truc Tran: Metabolism Branch, National Cancer Institute, National Institutes of Health
Xin Yu: Metabolism Branch, National Cancer Institute, National Institutes of Health
John I. Powell: Bioinformatics and Molecular Analysis Section, CBEL, CIT, NIH
Liming Yang: Bioinformatics and Molecular Analysis Section, CBEL, CIT, NIH
Gerald E. Marti: CBER, FDA
Troy Moore: Research Genetics
James Hudson: Research Genetics
Lisheng Lu: Pediatrics
David B. Lewis: Pediatrics
Robert Tibshirani: Health Research & Policy and Statistics
Gavin Sherlock: Life Sciences Division, Lawrence Orlando Berkeley National Labs and Department of Molecular and Cellular Biology, University of California
Wing C. Chan: Departments of Pathology and Microbiology
Timothy C. Greiner: Departments of Pathology and Microbiology
Dennis D. Weisenburger: Departments of Pathology and Microbiology
James O. Armitage: Internal Medicine, University of Nebraska Medical Center
Roger Warnke: Pathology
Ronald Levy: Medicine
Wyndham Wilson: Medicine Branch, National Cancer Institute, National Institutes of Health
Michael R. Grever: Johns Hopkins Oncology Center, Johns Hopkins School of Medicine
John C. Byrd: Walter Reed Army Medical Center
David Botstein: Life Sciences Division, Lawrence Orlando Berkeley National Labs and Department of Molecular and Cellular Biology, University of California
Patrick O. Brown: Departments of Biochemistry
Louis M. Staudt: Metabolism Branch, National Cancer Institute, National Institutes of Health

Nature, 2000, vol. 403, issue 6769, 503-511

Abstract: Abstract Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumours. Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumours of DLBCL patients, apparently reflecting the variation in tumour proliferation rate, host response and differentiation state of the tumour. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal centre B cells (‘germinal centre B-like DLBCL’); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells (‘activated B-like DLBCL’). Patients with germinal centre B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumours on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer.

Date: 2000
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DOI: 10.1038/35000501

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