Title: BMI1, The polycomb-group gene, is recurrently targeted by genomic rearrangements in progressive B-cell leukemia/lymphoma
Authors: Rouhigharabaei, Leila
Ferreiro, Julio Finalet
Put, Natalie
Michaux, Lucienne
Tousseyn, Thomas
Lefebvre, Christine
Gardiner, Anne
De Kelver, Wim
Demuynck, Hilde
Verschuere, Johan
Théate, Ivan
Vicente, Carmen
Vandenberghe, Peter
Cools, Jan
Wlodarska, Iwona # ×
Issue Date: Oct-2013
Publisher: Wiley-Liss, Inc.
Series Title: Genes, chromosomes & cancer vol:52 issue:10 pages:928-944
Article number: 10.1002/gcc.22088
Abstract: BMI1, a Polycomb-group gene located at 10p12.2, is implicated in the pathogenesis of a variety of tumors. However, the genetic molecular mechanisms underlying its aberrant expression in cancer cells remain largely unknown. In this study, we show that BMI1 is recurrently targeted by chromosomal aberrations in B-cell leukemia/lymphoma. We identified a novel t(10;14)(p12;q32)/IGH-BMI1 rearrangement and its IGL variant in six cases of chronic lymphocytic leukemia (CLL) and found that these aberrations were consistently acquired at time of disease progression and high grade transformation of leukemia (Richter syndrome). The IG-BMI1 translocations were not associated with any particular molecular subtype of CLL and the leukemias were negative for common mutations of NOTCH1 and TP53, known to increase a risk of progression and transformation in CLL. In addition, using FISH and SNP array analysis, we identified a wide range of BMI1-involving 10p12 lesions in 17 cases of mantle cell lymphoma (MCL). These aberrations included various balanced and unbalanced structural abnormalities and very frequently but not exclusively, were associated with gain of the BMI1 locus and loss of the 10p terminal sequences. These findings point to genomic instability at the 10p region in MCL which likely promotes rearrangements and deregulation of BMI1. Our findings are in line with previously published observations correlating overexpression of BMI1 with tumor progression and chemoresistance. In summary, our study provides new insights into genetic molecular mechanisms underlying aberrant expression of BMI1 in lymphoma and documents its contribution in the pathogenesis of Richter syndrome and MCL. © 2013 Wiley Periodicals, Inc.
ISSN: 1045-2257
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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