The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma

Andreas Rosenwald, George Wright, Wing C. Chan, Joseph M. Connors, Elias Campo, Richard I. Fisher, Randy D. Gascoyne, H. Konrad Muller-Hermelink, Erlend B. Smeland, Jena M. Giltnane, Elaine M. Hurt, Hong Zhao, Lauren Averett, Liming Yang, Wyndham H. Wilson, Elaine S. Jaffe, Richard Simon, Richard D. Klausner, John Powell, Patricia L. DuffeyDan L. Longo, Timothy C. Greiner, Dennis D. Weisenburger, Warren G. Sanger, Bhavana J. Dave, James C. Lynch, Julie Vose, James O. Armitage, Emilio Montserrat, Armando López-Guillermo, Thomas M. Grogan, Thomas P Miller, Michel Leblanc, German Ott, Stein Kvaloy, Jan Delabie, Harald Holte, Peter Krajci, Trond Stokke, Louis M. Staudt

Research output: Contribution to journalArticle

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Abstract

Background: The survival of patients with diffuse large-B-cell lymphoma after chemotherapy is influenced by molecular features of the tumors. We used the gene-expression profiles of these lymphomas to develop a molecular predictor of survival. Methods: Biopsy samples of diffuse large-B-cell lymphoma from 240 patients were examined for gene expression with the use of DNA microarrays and analyzed for genomic abnormalities. Subgroups with distinctive gene-expression profiles were defined on the basis of hierarchical clustering. A molecular predictor of risk was constructed with the use of genes with expression patterns that were associated with survival in a preliminary group of 160 patients and was then tested in a validation group of 80 patients. The accuracy of this predictor was compared with that of the international prognostic index. Results: Three gene-expression subgroups - germinal-center B-cell-like, activated B-cell-like, and type 3 diffuse large-B-cell lymphoma - were identified. Two common oncogenic events in diffuse large-B-cell lymphoma, bcl-2 translocation and c-rel amplification, were detected only in the germinal-center B-cell-like subgroup. Patients in this subgroup had the highest five-year survival rate. To identify other molecular determinants of outcome, we searched for individual genes with expression patterns that correlated with survival in the preliminary group of patients. Most of these genes fell within four gene-expression signatures characteristic of germinal-center B cells, proliferating cells, reactive stromal and immune cells in the lymph node, or major-histocompatibility-complex class II complex. We used 17 genes to construct a predictor of overall survival after chemotherapy. This gene-based predictor and the international prognostic index were independent prognostic indicators. Conclusions: DNA microarrays can be used to formulate a molecular predictor of survival after chemotherapy for diffuse large-B-cell lymphoma.

Original languageEnglish (US)
Pages (from-to)1937-1947
Number of pages11
JournalNew England Journal of Medicine
Volume346
Issue number25
DOIs
StatePublished - Jun 20 2002

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Lymphoma, Large B-Cell, Diffuse
Drug Therapy
Germinal Center
Survival
B-Lymphocytes
Transcriptome
Gene Expression
Oligonucleotide Array Sequence Analysis
Genes
Stromal Cells
Major Histocompatibility Complex
Cluster Analysis
Lymphoma
Survival Rate
Lymph Nodes
Biopsy
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Rosenwald, A., Wright, G., Chan, W. C., Connors, J. M., Campo, E., Fisher, R. I., ... Staudt, L. M. (2002). The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. New England Journal of Medicine, 346(25), 1937-1947. https://doi.org/10.1056/NEJMoa012914

The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. / Rosenwald, Andreas; Wright, George; Chan, Wing C.; Connors, Joseph M.; Campo, Elias; Fisher, Richard I.; Gascoyne, Randy D.; Konrad Muller-Hermelink, H.; Smeland, Erlend B.; Giltnane, Jena M.; Hurt, Elaine M.; Zhao, Hong; Averett, Lauren; Yang, Liming; Wilson, Wyndham H.; Jaffe, Elaine S.; Simon, Richard; Klausner, Richard D.; Powell, John; Duffey, Patricia L.; Longo, Dan L.; Greiner, Timothy C.; Weisenburger, Dennis D.; Sanger, Warren G.; Dave, Bhavana J.; Lynch, James C.; Vose, Julie; Armitage, James O.; Montserrat, Emilio; López-Guillermo, Armando; Grogan, Thomas M.; Miller, Thomas P; Leblanc, Michel; Ott, German; Kvaloy, Stein; Delabie, Jan; Holte, Harald; Krajci, Peter; Stokke, Trond; Staudt, Louis M.

In: New England Journal of Medicine, Vol. 346, No. 25, 20.06.2002, p. 1937-1947.

Research output: Contribution to journalArticle

Rosenwald, A, Wright, G, Chan, WC, Connors, JM, Campo, E, Fisher, RI, Gascoyne, RD, Konrad Muller-Hermelink, H, Smeland, EB, Giltnane, JM, Hurt, EM, Zhao, H, Averett, L, Yang, L, Wilson, WH, Jaffe, ES, Simon, R, Klausner, RD, Powell, J, Duffey, PL, Longo, DL, Greiner, TC, Weisenburger, DD, Sanger, WG, Dave, BJ, Lynch, JC, Vose, J, Armitage, JO, Montserrat, E, López-Guillermo, A, Grogan, TM, Miller, TP, Leblanc, M, Ott, G, Kvaloy, S, Delabie, J, Holte, H, Krajci, P, Stokke, T & Staudt, LM 2002, 'The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma', New England Journal of Medicine, vol. 346, no. 25, pp. 1937-1947. https://doi.org/10.1056/NEJMoa012914
Rosenwald, Andreas ; Wright, George ; Chan, Wing C. ; Connors, Joseph M. ; Campo, Elias ; Fisher, Richard I. ; Gascoyne, Randy D. ; Konrad Muller-Hermelink, H. ; Smeland, Erlend B. ; Giltnane, Jena M. ; Hurt, Elaine M. ; Zhao, Hong ; Averett, Lauren ; Yang, Liming ; Wilson, Wyndham H. ; Jaffe, Elaine S. ; Simon, Richard ; Klausner, Richard D. ; Powell, John ; Duffey, Patricia L. ; Longo, Dan L. ; Greiner, Timothy C. ; Weisenburger, Dennis D. ; Sanger, Warren G. ; Dave, Bhavana J. ; Lynch, James C. ; Vose, Julie ; Armitage, James O. ; Montserrat, Emilio ; López-Guillermo, Armando ; Grogan, Thomas M. ; Miller, Thomas P ; Leblanc, Michel ; Ott, German ; Kvaloy, Stein ; Delabie, Jan ; Holte, Harald ; Krajci, Peter ; Stokke, Trond ; Staudt, Louis M. / The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. In: New England Journal of Medicine. 2002 ; Vol. 346, No. 25. pp. 1937-1947.
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title = "The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma",
abstract = "Background: The survival of patients with diffuse large-B-cell lymphoma after chemotherapy is influenced by molecular features of the tumors. We used the gene-expression profiles of these lymphomas to develop a molecular predictor of survival. Methods: Biopsy samples of diffuse large-B-cell lymphoma from 240 patients were examined for gene expression with the use of DNA microarrays and analyzed for genomic abnormalities. Subgroups with distinctive gene-expression profiles were defined on the basis of hierarchical clustering. A molecular predictor of risk was constructed with the use of genes with expression patterns that were associated with survival in a preliminary group of 160 patients and was then tested in a validation group of 80 patients. The accuracy of this predictor was compared with that of the international prognostic index. Results: Three gene-expression subgroups - germinal-center B-cell-like, activated B-cell-like, and type 3 diffuse large-B-cell lymphoma - were identified. Two common oncogenic events in diffuse large-B-cell lymphoma, bcl-2 translocation and c-rel amplification, were detected only in the germinal-center B-cell-like subgroup. Patients in this subgroup had the highest five-year survival rate. To identify other molecular determinants of outcome, we searched for individual genes with expression patterns that correlated with survival in the preliminary group of patients. Most of these genes fell within four gene-expression signatures characteristic of germinal-center B cells, proliferating cells, reactive stromal and immune cells in the lymph node, or major-histocompatibility-complex class II complex. We used 17 genes to construct a predictor of overall survival after chemotherapy. This gene-based predictor and the international prognostic index were independent prognostic indicators. Conclusions: DNA microarrays can be used to formulate a molecular predictor of survival after chemotherapy for diffuse large-B-cell lymphoma.",
author = "Andreas Rosenwald and George Wright and Chan, {Wing C.} and Connors, {Joseph M.} and Elias Campo and Fisher, {Richard I.} and Gascoyne, {Randy D.} and {Konrad Muller-Hermelink}, H. and Smeland, {Erlend B.} and Giltnane, {Jena M.} and Hurt, {Elaine M.} and Hong Zhao and Lauren Averett and Liming Yang and Wilson, {Wyndham H.} and Jaffe, {Elaine S.} and Richard Simon and Klausner, {Richard D.} and John Powell and Duffey, {Patricia L.} and Longo, {Dan L.} and Greiner, {Timothy C.} and Weisenburger, {Dennis D.} and Sanger, {Warren G.} and Dave, {Bhavana J.} and Lynch, {James C.} and Julie Vose and Armitage, {James O.} and Emilio Montserrat and Armando L{\'o}pez-Guillermo and Grogan, {Thomas M.} and Miller, {Thomas P} and Michel Leblanc and German Ott and Stein Kvaloy and Jan Delabie and Harald Holte and Peter Krajci and Trond Stokke and Staudt, {Louis M.}",
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TY - JOUR

T1 - The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma

AU - Rosenwald, Andreas

AU - Wright, George

AU - Chan, Wing C.

AU - Connors, Joseph M.

AU - Campo, Elias

AU - Fisher, Richard I.

AU - Gascoyne, Randy D.

AU - Konrad Muller-Hermelink, H.

AU - Smeland, Erlend B.

AU - Giltnane, Jena M.

AU - Hurt, Elaine M.

AU - Zhao, Hong

AU - Averett, Lauren

AU - Yang, Liming

AU - Wilson, Wyndham H.

AU - Jaffe, Elaine S.

AU - Simon, Richard

AU - Klausner, Richard D.

AU - Powell, John

AU - Duffey, Patricia L.

AU - Longo, Dan L.

AU - Greiner, Timothy C.

AU - Weisenburger, Dennis D.

AU - Sanger, Warren G.

AU - Dave, Bhavana J.

AU - Lynch, James C.

AU - Vose, Julie

AU - Armitage, James O.

AU - Montserrat, Emilio

AU - López-Guillermo, Armando

AU - Grogan, Thomas M.

AU - Miller, Thomas P

AU - Leblanc, Michel

AU - Ott, German

AU - Kvaloy, Stein

AU - Delabie, Jan

AU - Holte, Harald

AU - Krajci, Peter

AU - Stokke, Trond

AU - Staudt, Louis M.

PY - 2002/6/20

Y1 - 2002/6/20

N2 - Background: The survival of patients with diffuse large-B-cell lymphoma after chemotherapy is influenced by molecular features of the tumors. We used the gene-expression profiles of these lymphomas to develop a molecular predictor of survival. Methods: Biopsy samples of diffuse large-B-cell lymphoma from 240 patients were examined for gene expression with the use of DNA microarrays and analyzed for genomic abnormalities. Subgroups with distinctive gene-expression profiles were defined on the basis of hierarchical clustering. A molecular predictor of risk was constructed with the use of genes with expression patterns that were associated with survival in a preliminary group of 160 patients and was then tested in a validation group of 80 patients. The accuracy of this predictor was compared with that of the international prognostic index. Results: Three gene-expression subgroups - germinal-center B-cell-like, activated B-cell-like, and type 3 diffuse large-B-cell lymphoma - were identified. Two common oncogenic events in diffuse large-B-cell lymphoma, bcl-2 translocation and c-rel amplification, were detected only in the germinal-center B-cell-like subgroup. Patients in this subgroup had the highest five-year survival rate. To identify other molecular determinants of outcome, we searched for individual genes with expression patterns that correlated with survival in the preliminary group of patients. Most of these genes fell within four gene-expression signatures characteristic of germinal-center B cells, proliferating cells, reactive stromal and immune cells in the lymph node, or major-histocompatibility-complex class II complex. We used 17 genes to construct a predictor of overall survival after chemotherapy. This gene-based predictor and the international prognostic index were independent prognostic indicators. Conclusions: DNA microarrays can be used to formulate a molecular predictor of survival after chemotherapy for diffuse large-B-cell lymphoma.

AB - Background: The survival of patients with diffuse large-B-cell lymphoma after chemotherapy is influenced by molecular features of the tumors. We used the gene-expression profiles of these lymphomas to develop a molecular predictor of survival. Methods: Biopsy samples of diffuse large-B-cell lymphoma from 240 patients were examined for gene expression with the use of DNA microarrays and analyzed for genomic abnormalities. Subgroups with distinctive gene-expression profiles were defined on the basis of hierarchical clustering. A molecular predictor of risk was constructed with the use of genes with expression patterns that were associated with survival in a preliminary group of 160 patients and was then tested in a validation group of 80 patients. The accuracy of this predictor was compared with that of the international prognostic index. Results: Three gene-expression subgroups - germinal-center B-cell-like, activated B-cell-like, and type 3 diffuse large-B-cell lymphoma - were identified. Two common oncogenic events in diffuse large-B-cell lymphoma, bcl-2 translocation and c-rel amplification, were detected only in the germinal-center B-cell-like subgroup. Patients in this subgroup had the highest five-year survival rate. To identify other molecular determinants of outcome, we searched for individual genes with expression patterns that correlated with survival in the preliminary group of patients. Most of these genes fell within four gene-expression signatures characteristic of germinal-center B cells, proliferating cells, reactive stromal and immune cells in the lymph node, or major-histocompatibility-complex class II complex. We used 17 genes to construct a predictor of overall survival after chemotherapy. This gene-based predictor and the international prognostic index were independent prognostic indicators. Conclusions: DNA microarrays can be used to formulate a molecular predictor of survival after chemotherapy for diffuse large-B-cell lymphoma.

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U2 - 10.1056/NEJMoa012914

DO - 10.1056/NEJMoa012914

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AN - SCOPUS:0037142053

VL - 346

SP - 1937

EP - 1947

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 25

ER -