Transformation of follicular lymphoma to diffuse large B-cell lymphoma proceeds by distinct oncogenic mechanisms

Andrew J. Davies, Andreas Rosenwald, George Wright, Abigail Lee, Kim W. Last, Dennis D. Weisenburger, Wing C. Chan, Jan Delabie, Rita M. Braziel, Elias Campo, Randy D. Gascoyne, Elaine S. Jaffe, H. Konrad Muller-Hermelink, German Ott, Maria Calaminici, Andrew J. Norton, Lindsey K. Goff, Jude Fitzgibbon, Louis M. Staudt, T. Andrew Lister

Research output: Contribution to journalArticle

119 Scopus citations

Abstract

This study was undertaken to further elucidate the biological mechanisms underlying the frequent event of transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL). The gene expression profiles of 20 paired lymph node biopsies, derived from the same patient pre- and post-transformation, were analysed using the Lymphochip cDNA microarray. TP53 mutation analysis was performed and copy number alterations at the c-REL and CDNK2A examined. Immunohistochemistry was performed on an independent panel of paired transformation paraffin-embedded samples. Transformed follicular lymphoma was predominantly of the germinal centre B-like phenotype both at the mRNA and protein level. Despite this homogeneity, transformation proceeded by at least two pathways. One mechanism was characterised by high proliferation, as assessed by the co-ordinately expressed genes of the proliferation signature. This group was associated with the presence of recurrent oncogenic abnormalities. In the remaining cases, proliferation was not increased and transformation proceeded by alternative routes as yet undetermined. Genes involved in cellular proliferation prevailed amongst those that were significantly increased upon transformation and T cell and follicular dendritic-associated genes predominated amongst those that decreased. t-FL is a germinal centre B (GCB)-like malignancy that evolves by two pathways, one that is similar in proliferation rate to the antecedent FL and the other that has a higher proliferation rate and is characterised by the presence of recognised oncogenic abnormalities.

Original languageEnglish (US)
Pages (from-to)286-293
Number of pages8
JournalBritish Journal of Haematology
Volume136
Issue number2
DOIs
StatePublished - Jan 2007

Keywords

  • Diffuse large B-cell lymphoma
  • Expression profiling
  • Follicular lymphoma
  • Transformation

ASJC Scopus subject areas

  • Hematology

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