Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma.
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.
Rosenwald
Andreas
A
Metabolism Branch, National Cancer Institute, National Institute of Health, Bethesda, MD 20892, USA.
Wright
George
G
Leroy
Karen
K
Yu
Xin
X
Gaulard
Philippe
P
Gascoyne
Randy D
RD
Chan
Wing C
WC
Zhao
Tong
T
Haioun
Corinne
C
Greiner
Timothy C
TC
Weisenburger
Dennis D
DD
Lynch
James C
JC
Vose
Julie
J
Armitage
James O
JO
Smeland
Erlend B
EB
Kvaloy
Stein
S
Holte
Harald
H
Delabie
Jan
J
Campo
Elias
E
Montserrat
Emili
E
Lopez-Guillermo
Armando
A
Ott
German
G
Muller-Hermelink
H Konrad
HK
Connors
Joseph M
JM
Braziel
Rita
R
Grogan
Thomas M
TM
Fisher
Richard I
RI
Miller
Thomas P
TP
LeBlanc
Michael
M
Chiorazzi
Michael
M
Zhao
Hong
H
Yang
Liming
L
Powell
John
J
Wilson
Wyndham H
WH
Jaffe
Elaine S
ES
Simon
Richard
R
Klausner
Richard D
RD
Staudt
Louis M
LM
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