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

نویسندگان

  • 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
  • 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
چکیده

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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عنوان ژورنال:
  • Blood

دوره 106 9  شماره 

صفحات  -

تاریخ انتشار 2005