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.
authors.affiliation: Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md 20892, USA.
authors.forename: Andreas
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authors.lastname: Rosenwald
authors.forename: George
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authors.lastname: Wright
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
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authors.lastname: Campo
authors.forename: Richard I
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authors.lastname: Fisher
authors.forename: Randy D
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authors.forename: H Konrad
authors.initials: HK
authors.lastname: Muller-Hermelink
authors.forename: Erlend B
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authors.lastname: Smeland
authors.forename: Jena M
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authors.lastname: Hurt
authors.forename: Hong
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authors.lastname: Zhao
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authors.lastname: Averett
authors.forename: Liming
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authors.lastname: Yang
authors.forename: Wyndham H
authors.initials: WH
authors.lastname: Wilson
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Richard
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authors.lastname: Simon
authors.forename: Richard D
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authors.lastname: Klausner
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authors.lastname: Powell
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authors.lastname: Duffey
authors.forename: Dan L
authors.initials: DL
authors.lastname: Longo
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Greiner
authors.forename: Dennis D
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authors.lastname: Weisenburger
authors.forename: Warren G
authors.initials: WG
authors.lastname: Sanger
authors.forename: Bhavana J
authors.initials: BJ
authors.lastname: Dave
authors.forename: James C
authors.initials: JC
authors.lastname: Lynch
authors.forename: Julie
authors.initials: J
authors.lastname: Vose
authors.forename: James O
authors.initials: JO
authors.lastname: Armitage
authors.forename: Emilio
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authors.lastname: Montserrat
authors.forename: Armando
authors.initials: A
authors.lastname: López-Guillermo
authors.forename: Thomas M
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authors.lastname: Grogan
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Miller
authors.forename: Michel
authors.initials: M
authors.lastname: LeBlanc
authors.forename: German
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authors.lastname: Ott
authors.forename: Stein
authors.initials: S
authors.lastname: Kvaloy
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.forename: Harald
authors.initials: H
authors.lastname: Holte
authors.forename: Peter
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authors.lastname: Krajci
authors.forename: Trond
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authors.lastname: Stokke
authors.forename: Louis M
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mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001706:Biopsy; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D000903:Antibiotics, Antineoplastic