Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene-expression-based survival prediction

Silvia Bea, Andreas Zettl, George Wright, Itziar Salaverria, Philipp Jehn, Victor Moreno, Christof Burek, German Ott, Xavier Puig, Liming Yang, Armando Lopez-Guillermo, Wing C. Chan, Timothy C. Greiner, Dennis D. Weisenburger, James O. Armitage, Randy D. Gascoyne, Joseph M. Connors, Thomas M. Grogan, Rita Braziel, Richard I. Fisher & 13 others Erlend B. Smeland, Stein Kvaloy, Harald Holte, Jan Delabie, Richard Simon, John Powell, Wyndham H. Wilson, Elaine S. Jaffe, Emili Montserrat, Hans Konrad Muller-Hermelink, Louis M. Staudt, Elias Campo, Andreas Rosenwald

Research output: Contribution to journalArticle

294 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3183-3190
Number of pages8
JournalBlood
Volume106
Issue number9
DOIs
StatePublished - Nov 2005
Externally publishedYes

Fingerprint

Lymphoma, Large B-Cell, Diffuse
Gene expression
Tumors
Cells
Gene Expression
B-Lymphocytes
Neoplasms
Germinal Center
Transcriptome
Genes
Cytology
Comparative Genomic Hybridization
Gene Expression Profiling
Lymphoma
Aberrations
Amplification
Trisomy
Chromosome Aberrations
DNA
Cell Biology

ASJC Scopus subject areas

  • Hematology

Cite this

Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene-expression-based survival prediction. / Bea, Silvia; Zettl, Andreas; Wright, George; Salaverria, Itziar; Jehn, Philipp; Moreno, Victor; Burek, Christof; Ott, German; Puig, Xavier; Yang, Liming; Lopez-Guillermo, Armando; Chan, Wing C.; Greiner, Timothy C.; Weisenburger, Dennis D.; Armitage, James O.; Gascoyne, Randy D.; Connors, Joseph M.; Grogan, Thomas M.; Braziel, Rita; Fisher, Richard I.; Smeland, Erlend B.; Kvaloy, Stein; Holte, Harald; Delabie, Jan; Simon, Richard; Powell, John; Wilson, Wyndham H.; Jaffe, Elaine S.; Montserrat, Emili; Muller-Hermelink, Hans Konrad; Staudt, Louis M.; Campo, Elias; Rosenwald, Andreas.

In: Blood, Vol. 106, No. 9, 11.2005, p. 3183-3190.

Research output: Contribution to journalArticle

Bea, S, Zettl, A, Wright, G, Salaverria, I, Jehn, P, Moreno, V, Burek, C, Ott, G, Puig, X, Yang, L, Lopez-Guillermo, A, Chan, WC, Greiner, TC, Weisenburger, DD, Armitage, JO, Gascoyne, RD, Connors, JM, Grogan, TM, Braziel, R, Fisher, RI, Smeland, EB, Kvaloy, S, Holte, H, Delabie, J, Simon, R, Powell, J, Wilson, WH, Jaffe, ES, Montserrat, E, Muller-Hermelink, HK, Staudt, LM, Campo, E & Rosenwald, A 2005, 'Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene-expression-based survival prediction', Blood, vol. 106, no. 9, pp. 3183-3190. https://doi.org/10.1182/blood-2005-04-1399
Bea, Silvia ; Zettl, Andreas ; Wright, George ; Salaverria, Itziar ; Jehn, Philipp ; Moreno, Victor ; Burek, Christof ; Ott, German ; Puig, Xavier ; Yang, Liming ; Lopez-Guillermo, Armando ; Chan, Wing C. ; Greiner, Timothy C. ; Weisenburger, Dennis D. ; Armitage, James O. ; Gascoyne, Randy D. ; Connors, Joseph M. ; Grogan, Thomas M. ; Braziel, Rita ; Fisher, Richard I. ; Smeland, Erlend B. ; Kvaloy, Stein ; Holte, Harald ; Delabie, Jan ; Simon, Richard ; Powell, John ; Wilson, Wyndham H. ; Jaffe, Elaine S. ; Montserrat, Emili ; Muller-Hermelink, Hans Konrad ; Staudt, Louis M. ; Campo, Elias ; Rosenwald, Andreas. / Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene-expression-based survival prediction. In: Blood. 2005 ; Vol. 106, No. 9. pp. 3183-3190.
@article{bafe9e3bc2204d3a805e933a955daa9e,
title = "Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene-expression-based survival prediction",
abstract = "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.",
author = "Silvia Bea and Andreas Zettl and George Wright and Itziar Salaverria and Philipp Jehn and Victor Moreno and Christof Burek and German Ott and Xavier Puig and Liming Yang and Armando Lopez-Guillermo and Chan, {Wing C.} and Greiner, {Timothy C.} and Weisenburger, {Dennis D.} and Armitage, {James O.} and Gascoyne, {Randy D.} and Connors, {Joseph M.} and Grogan, {Thomas M.} and Rita Braziel and Fisher, {Richard I.} and Smeland, {Erlend B.} and Stein Kvaloy and Harald Holte and Jan Delabie and Richard Simon and John Powell and Wilson, {Wyndham H.} and Jaffe, {Elaine S.} and Emili Montserrat and Muller-Hermelink, {Hans Konrad} and Staudt, {Louis M.} and Elias Campo and Andreas Rosenwald",
year = "2005",
month = "11",
doi = "10.1182/blood-2005-04-1399",
language = "English (US)",
volume = "106",
pages = "3183--3190",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "9",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=27644488026&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27644488026&partnerID=8YFLogxK

U2 - 10.1182/blood-2005-04-1399

DO - 10.1182/blood-2005-04-1399

M3 - Article

VL - 106

SP - 3183

EP - 3190

JO - Blood

JF - Blood

SN - 0006-4971

IS - 9

ER -