Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations

Ellen Leich, Itziar Salaverria, Silvia Bea, Andreas Zettl, George Wright, Victor Moreno, Randy D. Gascoyne, Wing Chung Chan, Rita M. Braziel, Lisa M. Rimsza, Dennis D. Weisenburger, Jan Delabie, Elaine S. Jaffe, Andrew Lister, Jude Fitzgibbon, Louis M. Staudt, Elena M. Hartmann, Hans Konrad Mueller-Hermelink, Elias Campo, German OttAndreas Rosenwald

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Abstract

Follicular lymphoma (FL) is genetically characterized by the presence of the t(14;18)(q32; q21) chromosomal translocation in approximately 90% of cases. In contrast to FL carrying the t(14;18), their t(14;18)-negative counterparts are less well studied about their immunohistochemical, genetic, molecular, and clinical features. Within a previously published series of 184 FLs grades 1 to 3A with available gene expression data, we identified 17 FLs lacking the t(14;18). Comparative genomic hybridization and high-resolution single nucleotide polymorphism (SNP) array profiling showed that gains/amplifications of the BCL2 gene locus in 18q were restricted to the t(14;18)-positive FL subgroup. Acomparison of gene expression profiles showed an enrichment of germinal center B cell-associated signatures in t(14;18)-positive FL, whereas activated B cell-like, NFκB, proliferation, and bystander cell signatures were enriched in t(14;18)-negative FL. These findings were confirmed by immunohistochemistry in an independent validation series of 84 FLs, in which 32% of t(14;18)-negative FLs showed weak or absent CD10 expression and 91% an increased Ki67 proliferation rate. Although overall survival did not differ between FL with and without t(14;18), our findings suggest distinct molecular features of t(14;18)-negative FL.

Original languageEnglish (US)
Pages (from-to)826-834
Number of pages9
JournalBlood
Volume114
Issue number4
DOIs
StatePublished - Jan 1 2009

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Leich, E., Salaverria, I., Bea, S., Zettl, A., Wright, G., Moreno, V., Gascoyne, R. D., Chan, W. C., Braziel, R. M., Rimsza, L. M., Weisenburger, D. D., Delabie, J., Jaffe, E. S., Lister, A., Fitzgibbon, J., Staudt, L. M., Hartmann, E. M., Mueller-Hermelink, H. K., Campo, E., ... Rosenwald, A. (2009). Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations. Blood, 114(4), 826-834. https://doi.org/10.1182/blood-2009-01-198580