Translocations targeting CCND2, CCND3, and MYCN do occur in t(11;14)-negative mantle cell lymphomas

Blood. 2008 Jun 15;111(12):5683-90. doi: 10.1182/blood-2007-10-118794. Epub 2008 Apr 7.

Abstract

The genetics of t(11;14)(q13;q32)/cyclin D1-negative mantle cell lymphoma (MCL) is poorly understood. We report here 8 MCL cases lacking t(11;14) or variant CCND1 rearrangement that showed expression of cyclin D1 (2 cases), D2 (2 cases), and D3 (3 cases). One case was cyclin D negative. Cytogenetics and fluorescence in situ hybridization detected t(2;12)(p11;p13)/IGK-CCND2 in one of the cyclin D2-positive cases and t(6;14)(p21;q32)/IGH-CCND3 in one of the cyclin D3-positive cases. Moreover, we identified a novel cryptic t(2;14)(p24;q32) targeting MYCN in 2 blastoid MCLs: one negative for cyclin D and one expressing cyclin D3. Interestingly, both cases showed expression of cyclin E. Notably, all 3 blastoid MCLs showed a monoallelic deletion of RB1 associated with a lack of expression of RB1 protein and monoallelic loss of p16. In sum-mary, this study confirms frequent aberrant expression of cyclin D2 and D3 in t(11;14)-negative MCLs and shows a t(11;14)-independent expression of cy-clin D1 in 25% of present cases. Novel findings include cyclin E expression in 2 t(11;14)-negative MCLs characterized by a cryptic t(2;14)(p24;q32) and identification of MYCN as a new lymphoma oncogene associated with a blastoid MCL. Clinically important is a predisposition of t(11;14)-negative MCLs to the central nervous system involvement.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Chromosomes, Human, Pair 11
  • Chromosomes, Human, Pair 14
  • Cyclin D2
  • Cyclin D3
  • Cyclins / genetics*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genetic Variation
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lymphoma, Mantle-Cell / genetics*
  • Lymphoma, Mantle-Cell / pathology
  • Male
  • Middle Aged
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins / genetics*
  • Oncogene Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Translocation, Genetic*

Substances

  • CCND2 protein, human
  • CCND3 protein, human
  • Cyclin D2
  • Cyclin D3
  • Cyclins
  • MYCN protein, human
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins
  • Oncogene Proteins