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 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 journalArticle

7024 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)503-511
Number of pages9
JournalNature
Volume403
Issue number6769
DOIs
StatePublished - Feb 3 2000
Externally publishedYes

Fingerprint

Lymphoma, Large B-Cell, Diffuse
Gene Expression Profiling
Germinal Center
B-Lymphocytes
Neoplasms
Gene Expression
Survival
Oligonucleotide Array Sequence Analysis
Natural History
Non-Hodgkin's Lymphoma
Genes
Cell Differentiation
Blood Cells

ASJC Scopus subject areas

  • General

Cite this

Alizadeh, A. A., Elsen, M. B., Davis, R. E., Ma, C. L., Lossos, I., Rosenwald, A., ... Staudt, L. M. (2000). Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature, 403(6769), 503-511. https://doi.org/10.1038/35000501

Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. / Alizadeh, Ash A.; Elsen, Michael B.; Davis, R. Eric; Ma, Ch L.; Lossos, Izidore; Rosenwald, Andreas; Boldrick, Jennifer C.; Sabet, Hajeer; Tran, True; Yu, Xin; Powell, John I.; Yang, Liming; Marü, Gerald E.; Moore, Troy; Hudson, James; Lu, Lisheng; Lewis, David B.; Tibshirani, Robert; Sherlock, Gavin; Chan, Wing C.; Greiner, Timothy C.; Weisenburger, Dennis D.; Armitage, James O.; Warnke, Roger; Levy, Ronald; Wilson, Wyndham; Grever, Michael R.; Byrd, John C.; Botstein, David; Brown, Patrick O.; Staudt, Louis M.

In: Nature, Vol. 403, No. 6769, 03.02.2000, p. 503-511.

Research output: Contribution to journalArticle

Alizadeh, AA, Elsen, MB, Davis, RE, Ma, CL, Lossos, I, Rosenwald, A, Boldrick, JC, Sabet, H, Tran, T, Yu, X, Powell, JI, Yang, L, Marü, GE, Moore, T, Hudson, J, Lu, L, Lewis, DB, Tibshirani, R, Sherlock, G, Chan, WC, Greiner, TC, Weisenburger, DD, Armitage, JO, Warnke, R, Levy, R, Wilson, W, Grever, MR, Byrd, JC, Botstein, D, Brown, PO & Staudt, LM 2000, 'Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling', Nature, vol. 403, no. 6769, pp. 503-511. https://doi.org/10.1038/35000501
Alizadeh AA, Elsen MB, Davis RE, Ma CL, Lossos I, Rosenwald A et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000 Feb 3;403(6769):503-511. https://doi.org/10.1038/35000501
Alizadeh, Ash A. ; Elsen, Michael B. ; Davis, R. Eric ; Ma, Ch L. ; Lossos, Izidore ; Rosenwald, Andreas ; Boldrick, Jennifer C. ; Sabet, Hajeer ; Tran, True ; Yu, Xin ; Powell, John I. ; Yang, Liming ; Marü, Gerald E. ; Moore, Troy ; Hudson, James ; Lu, Lisheng ; Lewis, David B. ; Tibshirani, Robert ; Sherlock, Gavin ; Chan, Wing C. ; Greiner, Timothy C. ; Weisenburger, Dennis D. ; Armitage, James O. ; Warnke, Roger ; Levy, Ronald ; Wilson, Wyndham ; Grever, Michael R. ; Byrd, John C. ; Botstein, David ; Brown, Patrick O. ; Staudt, Louis M. / Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. In: Nature. 2000 ; Vol. 403, No. 6769. pp. 503-511.
@article{40a4eb2314da4685b80a7d9e95e5b447,
title = "Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling",
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.",
author = "Alizadeh, {Ash A.} and Elsen, {Michael B.} and Davis, {R. Eric} and Ma, {Ch L.} and Izidore Lossos and Andreas Rosenwald and Boldrick, {Jennifer C.} and Hajeer Sabet and True Tran and Xin Yu and Powell, {John I.} and Liming Yang and Mar{\"u}, {Gerald E.} and Troy Moore and James Hudson and Lisheng Lu and Lewis, {David B.} and Robert Tibshirani and Gavin Sherlock and Chan, {Wing C.} and Greiner, {Timothy C.} and Weisenburger, {Dennis D.} and Armitage, {James O.} and Roger Warnke and Ronald Levy and Wyndham Wilson and Grever, {Michael R.} and Byrd, {John C.} and David Botstein and Brown, {Patrick O.} and Staudt, {Louis M.}",
year = "2000",
month = "2",
day = "3",
doi = "10.1038/35000501",
language = "English",
volume = "403",
pages = "503--511",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "6769",

}

TY - JOUR

T1 - Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling

AU - Alizadeh, Ash A.

AU - Elsen, Michael B.

AU - Davis, R. Eric

AU - Ma, Ch L.

AU - Lossos, Izidore

AU - Rosenwald, Andreas

AU - Boldrick, Jennifer C.

AU - Sabet, Hajeer

AU - Tran, True

AU - Yu, Xin

AU - Powell, John I.

AU - Yang, Liming

AU - Marü, Gerald E.

AU - Moore, Troy

AU - Hudson, James

AU - Lu, Lisheng

AU - Lewis, David B.

AU - Tibshirani, Robert

AU - Sherlock, Gavin

AU - Chan, Wing C.

AU - Greiner, Timothy C.

AU - Weisenburger, Dennis D.

AU - Armitage, James O.

AU - Warnke, Roger

AU - Levy, Ronald

AU - Wilson, Wyndham

AU - Grever, Michael R.

AU - Byrd, John C.

AU - Botstein, David

AU - Brown, Patrick O.

AU - Staudt, Louis M.

PY - 2000/2/3

Y1 - 2000/2/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0034598746&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034598746&partnerID=8YFLogxK

U2 - 10.1038/35000501

DO - 10.1038/35000501

M3 - Article

C2 - 10676951

AN - SCOPUS:0034598746

VL - 403

SP - 503

EP - 511

JO - Nature

JF - Nature

SN - 0028-0836

IS - 6769

ER -