MYC translocation and an increased copy number predict poor prognosis in adult diffuse large B-cell lymphoma (DLBCL), especially in germinal centre-like B cell (GCB) type

Histopathology. 2008 Aug;53(2):205-17. doi: 10.1111/j.1365-2559.2008.03076.x.

Abstract

Aims: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with various genetic alterations. The aim was to investigate MYC, Bcl-2 and Bcl-6 translocations and copy number changes in adult DLBCLs to evaluate their clinicopathological features and prognostic implications.

Methods and results: Gene status was examined using fluorescence in situ hybridization (FISH), and the results were analysed in the context of germinal centre B-cell (GCB) and non-GCB type of DLBCL based on immunohistochemistry. MYC translocation was observed in 9% (14 of 156), and an increased copy number (ICN) in 7.1% (11 of 156). MYC translocation was more common in GCB type (22%) than in non-GCB type (4.9%), and associated with advanced International Prognostic Index (IPI). MYC aberration, i.e. translocation or increased copy number (ICN), was significantly associated with shorter overall survival, especially for the GCB type. Bcl-2 translocation was rare (3.4%, five of 145), and ICN was observed in 11.7% (17 of 145), more frequently in non-GCB type (16%) than in GCB type (2.5%). Bcl-2 aberration tended to have an adverse effect on survival. In multivariate analysis, MYC ICN was an independent poor prognostic factor.

Conclusions: Analyses of MYC and Bcl-2 status, i.e. translocation and ICN, in the context of DLBCL phenotype might help predict prognosis and determine therapeutic strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B-Lymphocytes / pathology
  • Female
  • Gene Dosage*
  • Germinal Center / pathology*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lymphoma, Large B-Cell, Diffuse / diagnosis*
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-6 / genetics
  • Proto-Oncogene Proteins c-myc / genetics*
  • Translocation, Genetic*

Substances

  • MYC protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-bcl-6
  • Proto-Oncogene Proteins c-myc