Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene-expression-based survival prediction.
Gene-expression profiling has identified 3 major subgroups of diffuse large B-cell lymphoma (DLBCL): germinal center B-cell-like (GCB), activated B-cell-like (ABC), and primary mediastinal DLBCL (PMBCL). Using comparative genomic hybridization (CGH), we investigated the genetic alterations of 224 cases of untreated DLBCL (87 GCB-DLBCL, 77 ABC-DLBCL, 19 PMBCL, and 41 unclassified DLBCL) previously characterized by gene-expression profiling. The DLBCL subgroups differed significantly in the frequency of particular chromosomal aberrations. ABC-DLBCL had frequent trisomy 3, gains of 3q and 18q21-q22, and losses of 6q21-q22, whereas GCB-DLBCL had frequent gains of 12q12, and PMBCL had gains of 9p21-pter and 2p14-p16. Parallel analysis of CGH alterations, locus-specific gene-expression profiles, and global gene-expression signatures revealed that DNA amplifications and gains had a substantial impact on the expression of genes in the involved chromosomal regions, and some genes were overexpressed in a DLBCL subgroup-specific fashion. Unexpectedly, specific chromosomal alterations were associated with significant changes in gene-expression signatures that reflect various aspects of lymphoma cell biology as well as the host response to the lymphoma. In addition, gains involving the chromosomal region 3p11-p12 provided prognostic information that was statistically independent of the previously defined gene-expression-based survival model, thereby improving its predictive power.
Bea
Silvia
S
Department of Pathology and Hematology Hospital Clinic, University of Barcelona, Spain.
Zettl
Andreas
A
Wright
George
G
Salaverria
Itziar
I
Jehn
Philipp
P
Moreno
Victor
V
Burek
Christof
C
Ott
German
G
Puig
Xavier
X
Yang
Liming
L
Lopez-Guillermo
Armando
A
Chan
Wing C
WC
Greiner
Timothy C
TC
Weisenburger
Dennis D
DD
Armitage
James O
JO
Gascoyne
Randy D
RD
Connors
Joseph M
JM
Grogan
Thomas M
TM
Braziel
Rita
R
Fisher
Richard I
RI
Smeland
Erlend B
EB
Kvaloy
Stein
S
Holte
Harald
H
Delabie
Jan
J
Simon
Richard
R
Powell
John
J
Wilson
Wyndham H
WH
Jaffe
Elaine S
ES
Montserrat
Emili
E
Muller-Hermelink
Hans-Konrad
HK
Staudt
Louis M
LM
Campo
Elias
E
Rosenwald
Andreas
A
D002877:Chromosomes, Human / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D011237:Predictive Value of Tests; D011379:Prognosis; D015996:Survival Rate