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

Ash A. Alizadeh, Michael B. Elsen, R. Eric Davis, Ch L. Ma, Izidore S. Lossos, Andreas Rosenwald, Jennifer C. Boldrick, Hajeer Sabet, True Tran, Xin Yu, John I. Powell, Liming Yang, Gerald E. Marü, Troy Moore, James Hudson, Lisheng Lu, David B. Lewis, Robert Tibshirani, Gavin Sherlock, Wing C. ChanTimothy 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, Louis M. Staudt

Research output: Contribution to journalArticlepeer-review

8351 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)503-511
Number of pages9
Issue number6769
StatePublished - Feb 3 2000

ASJC Scopus subject areas

  • General


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