4th Palermo Conference on INNOVATIVE THERAPIES FOR LYMPHOID MALIGNANCIES
Published online 19 May 2009
Haematologica, Vol 94, Issue 7, 1020-1023 doi:10.3324/haematol.2008.000968
Copyright © 2009 by Ferrata Storti Foundation
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Malignant Lymphomas

Identification of the gene encoding cyclin E1 (CCNE1) as a novel IGH translocation partner in t(14;19)(q32;q12) in diffuse large B-cell lymphoma

Inga Nagel1, Takashi Akasaka2, Wolfram Klapper3, Stefan Gesk1, Sebastian Böttcher4, Matthias Ritgen4, Lana Harder1, Michael Kneba4, Martin J.S. Dyer2, Reiner Siebert1

1 Institute of Human Genetics, Christian-Albrechts University Kiel, University Hospital Schleswig-Holstein, Campus Kiel, Germany;
2 MRC Toxicology Unit/Leicester University, UK;
3 Department of Pathology, Christian-Albrechts University Kiel, University Hospital Schleswig-Holstein, Campus Kiel, Germany and
4 Second Department of Internal Medicine, Christian-Albrechts University Kiel, University Hospital Schleswig Holstein, Campus Kiel, Germany

Correspondence: Inga Nagel, Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 24, 24105 Kiel, Germany. E-mail:inagel{at}medgen.uni-kiel.de

In a subset of B-cell malignancies, the genes encoding members of the cyclin D familiy are juxtaposed to immunoglobulin loci through recurrent chromosomal translocations. Here, we identified the gene encoding cyclin E1 as novel translocation partner of the immunoglobulin heavy chain (IGH) locus involved in a t(14;19)(q32;q12) in a case of t(8;14)(q24;q32) IGH-MYC-positive leukemic diffuse large B-cell lymphoma. The translocation breakpoints were cloned and mapped to the switch region S{alpha}1 of IGH in 14q32 and approximately 60kb centromeric to CCNE1 in 19q12. Immunohistochemical analysis revealed overexpression of the cyclin E1 protein in this case, which to a comparable extent was observed in 3/41 independent DLBCL. These data indicate that cyclin E1 may act as a novel oncogene in B-cell lymphomagenesis.

Key words: cyclin E1, diffuse large B-cell lymphoma, IGH, MYC, translocation.