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.
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, California 94305, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Alizadeh
authors.forename: M B
authors.initials: MB
authors.lastname: Eisen
authors.forename: R E
authors.initials: RE
authors.lastname: Davis
authors.forename: C
authors.initials: C
authors.lastname: Ma
authors.forename: I S
authors.initials: IS
authors.lastname: Lossos
authors.forename: A
authors.initials: A
authors.lastname: Rosenwald
authors.forename: J C
authors.initials: JC
authors.lastname: Boldrick
authors.forename: H
authors.initials: H
authors.lastname: Sabet
authors.forename: T
authors.initials: T
authors.lastname: Tran
authors.forename: X
authors.initials: X
authors.lastname: Yu
authors.forename: J I
authors.initials: JI
authors.lastname: Powell
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.forename: G E
authors.initials: GE
authors.lastname: Marti
authors.forename: T
authors.initials: T
authors.lastname: Moore
authors.forename: J
authors.initials: J
authors.lastname: Hudson
authors.forename: L
authors.initials: L
authors.lastname: Lu
authors.forename: D B
authors.initials: DB
authors.lastname: Lewis
authors.forename: R
authors.initials: R
authors.lastname: Tibshirani
authors.forename: G
authors.initials: G
authors.lastname: Sherlock
authors.forename: W C
authors.initials: WC
authors.lastname: Chan
authors.forename: T C
authors.initials: TC
authors.lastname: Greiner
authors.forename: D D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: J O
authors.initials: JO
authors.lastname: Armitage
authors.forename: R
authors.initials: R
authors.lastname: Warnke
authors.forename: R
authors.initials: R
authors.lastname: Levy
authors.forename: W
authors.initials: W
authors.lastname: Wilson
authors.forename: M R
authors.initials: MR
authors.lastname: Grever
authors.forename: J C
authors.initials: JC
authors.lastname: Byrd
authors.forename: D
authors.initials: D
authors.lastname: Botstein
authors.forename: P O
authors.initials: PO
authors.lastname: Brown
authors.forename: L M
authors.initials: LM
authors.lastname: Staudt
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D014407:Tumor Cells, Cultured