TY - JOUR
T1 - Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene-expression-based survival prediction
AU - Bea, Silvia
AU - Zettl, Andreas
AU - Wright, George
AU - Salaverria, Itziar
AU - Jehn, Philipp
AU - Moreno, Victor
AU - Burek, Christof
AU - Ott, German
AU - Puig, Xavier
AU - Yang, Liming
AU - Lopez-Guillermo, Armando
AU - Chan, Wing C.
AU - Greiner, Timothy C.
AU - Weisenburger, Dennis D.
AU - Armitage, James O.
AU - Gascoyne, Randy D.
AU - Connors, Joseph M.
AU - Grogan, Thomas M.
AU - Braziel, Rita
AU - Fisher, Richard I.
AU - Smeland, Erlend B.
AU - Kvaloy, Stein
AU - Holte, Harald
AU - Delabie, Jan
AU - Simon, Richard
AU - Powell, John
AU - Wilson, Wyndham H.
AU - Jaffe, Elaine S.
AU - Montserrat, Emili
AU - Muller-Hermelink, Hans Konrad
AU - Staudt, Louis M.
AU - Campo, Elias
AU - Rosenwald, Andreas
PY - 2005/11
Y1 - 2005/11
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2005-04-1399
DO - 10.1182/blood-2005-04-1399
M3 - Article
C2 - 16046532
AN - SCOPUS:27644488026
SN - 0006-4971
VL - 106
SP - 3183
EP - 3190
JO - Blood
JF - Blood
IS - 9
ER -