title: Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma.
abstract: Using current diagnostic criteria, primary mediastinal B cell lymphoma (PMBL) cannot be distinguished from other types of diffuse large B cell lymphoma (DLBCL) reliably. We used gene expression profiling to develop a more precise molecular diagnosis of PMBL. PMBL patients were considerably younger than other DLBCL patients, and their lymphomas frequently involved other thoracic structures but not extrathoracic sites typical of other DLBCLs. PMBL patients had a relatively favorable clinical outcome, with a 5-yr survival rate of 64% compared with 46% for other DLBCL patients. Gene expression profiling strongly supported a relationship between PMBL and Hodgkin lymphoma: over one third of the genes that were more highly expressed in PMBL than in other DLBCLs were also characteristically expressed in Hodgkin lymphoma cells. PDL2, which encodes a regulator of T cell activation, was the gene that best discriminated PMBL from other DLBCLs and was also highly expressed in Hodgkin lymphoma cells. The genomic loci for PDL2 and several neighboring genes were amplified in over half of the PMBLs and in Hodgkin lymphoma cell lines. The molecular diagnosis of PMBL should significantly aid in the development of therapies tailored to this clinically and pathogenetically distinctive subgroup of DLBCL.
authors.affiliation: Metabolism Branch, National Cancer Institute, National Institute of Health, Bethesda, MD 20892, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: George
authors.initials: G
authors.lastname: Wright
authors.forename: Karen
authors.initials: K
authors.lastname: Leroy
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.forename: Philippe
authors.initials: P
authors.lastname: Gaulard
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
authors.forename: Tong
authors.initials: T
authors.lastname: Zhao
authors.forename: Corinne
authors.initials: C
authors.lastname: Haioun
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Greiner
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
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: Erlend B
authors.initials: EB
authors.lastname: Smeland
authors.forename: Stein
authors.initials: S
authors.lastname: Kvaloy
authors.forename: Harald
authors.initials: H
authors.lastname: Holte
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Emili
authors.initials: E
authors.lastname: Montserrat
authors.forename: Armando
authors.initials: A
authors.lastname: Lopez-Guillermo
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: H Konrad
authors.initials: HK
authors.lastname: Muller-Hermelink
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.forename: Rita
authors.initials: R
authors.lastname: Braziel
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Grogan
authors.forename: Richard I
authors.initials: RI
authors.lastname: Fisher
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Miller
authors.forename: Michael
authors.initials: M
authors.lastname: LeBlanc
authors.forename: Michael
authors.initials: M
authors.lastname: Chiorazzi
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Liming
authors.initials: L
authors.lastname: Yang
authors.forename: John
authors.initials: J
authors.lastname: Powell
authors.forename: Wyndham H
authors.initials: WH
authors.lastname: Wilson
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Richard
authors.initials: R
authors.lastname: Simon
authors.forename: Richard D
authors.initials: RD
authors.lastname: Klausner
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
mesh_terms: D000328:Adult; D002888:Chromosomes, Human, Pair 19; D003937:Diagnosis, Differential; D020869:Gene Expression Profiling; D006689:Hodgkin Disease / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006801:Humans; D016393:Lymphoma, B-Cell / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000235:genetics*; D008479:Mediastinal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D020411:Oligonucleotide Array Sequence Analysis; D015996:Survival Rate; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured