Sequence data reported in this article were deposited with the GenBank Database under Accession nos. AY496263–AY496267 (ARHGAP20) and AY497046–AY497060 (BRWD3).
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Research Article
Article first published online: 12 NOV 2004
DOI: 10.1002/gcc.20131
Copyright © 2004 Wiley-Liss, Inc.
Additional Information
How to Cite
Kalla, C., Nentwich, H., Schlotter, M., Mertens, D., Wildenberger, K., Döhner, H., Stilgenbauer, S. and Lichter, P. (2005), Translocation t(X;11)(q13;q23) in B-cell chronic lymphocytic leukemia disrupts two novel genes. Genes, Chromosomes and Cancer, 42: 128–143. doi: 10.1002/gcc.20131
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Approved designation of both novel genes, ARHGAP20, at 11q23, and BRWD3, at Xq13, was obtained from the HUGO Nomenclature Committee.
Publication History
- Issue published online: 8 DEC 2004
- Article first published online: 12 NOV 2004
- Manuscript Accepted: 28 SEP 2004
- Manuscript Received: 10 MAY 2004
Funded by
- Bundesministerium für Bildung und Forschung. Grant Number: 01KW9935
- Deutsche Krebshilfe. Grant Number: 70-3183-Li
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Abstract
Deletion of chromosome region 11q22–q23 defines a subgroup of patients with B-cell chronic lymphocytic leukemia (B-CLL) characterized by poor survival. Although the tumor-suppressor gene ATM in the consensus deletion region was found to be biallelically inactivated in about one third of B-CLL cases, in the majority of those who have this deletion, inactivation of the remaining ATM allele was not observed. To identify a second disease-associated gene, we investigated two B-CLL cases with translocation breakpoints in the critical 11q23 deletion region. In one case, a t(X;11)(q13;q23) was cloned and two novel genes were isolated. The breakpoint on 11q23 affected the ARHGAP20 gene, which encodes a protein predicted to be involved in the regulation of Rho family GTPases. The breakpoint on Xq13 occurred in BRWD3, which codes for a putative novel transcription factor. The rearrangement of ARHGAP20 and BRWD3 did not result in fusion transcripts, but it disrupted both genes. Mutation analysis of 28 B-CLL samples with monoallelic deletions and two B-CLL samples with 11q23 translocations detected no deleterious mutation in the remaining copy of ARHGAP20. Quantitative expression analysis in 22 B-CLLs revealed significant up-regulation of ARHGAP20 in CLL B cells, whereas BRWD3 was slightly down-regulated. Thus, deregulation of ARHGAP20 by altered gene expression or by gene disruption (but not point mutation) might be a general molecular mechanism of B-CLL leukemogenesis. © 2004 Wiley-Liss, Inc.