Human Molecular Genetics Advance Access originally published online on June 30, 2004
Human Molecular Genetics 2004 13(17):1827-1837; doi:10.1093/hmg/ddh195
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Human Molecular Genetics, Vol. 13, No. 17 © Oxford University Press 2004; all rights reserved
Comprehensive whole genome array CGH profiling of mantle cell lymphoma model genomes
1Department of Cancer Genetics, 2Department of Medical Oncology, 3Department of Pathology, British Columbia Cancer Agency, Vancouver, BC, Canada, 4Institute of Pathology, University of Wuerzburg, Germany, 5Center for Cancer Research, National Cancer Institute, Bethesda, MA, USA, 6MRC Toxicology Unit, University of Leicester, UK and 7Department of Hematology and Medical Oncology, Hospital Clinico, University of Valencia, Spain
Received May 1, 2004; Accepted June 15, 2004
Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin's lymphoma with median patient survival times of
3 years. Although the characteristic t(11;14)(q13;q32) is found in virtually all cases, experimental evidence suggests that this event alone is insufficient to result in lymphoma and secondary genomic alterations are required. Using a newly developed DNA microarray of 32 433 overlapping genomic segments spanning the entire human genome, we can for the first time move beyond marker based analysis and comprehensively search for secondary genomic alterations concomitant with the t(11;14) in eight commonly used cell models of MCL (Granta-519, HBL-2, NCEB-1, Rec-1, SP49, UPN-1, Z138C and JVM-2). Examining these genomes at tiling resolution identified an unexpected average of 35 genetic alterations per cell line, with equal numbers of amplifications and deletions. Recurrent high-level amplifications were identified at 18q21 containing BCL2, and at 13q31 containing GPC5. In addition, a recurrent homozygous deletion was identified at 9p21 containing p15 and p16. Alignment of these profiles revealed 14 recurrent losses and 21 recurrent gains as small as 130 kb. Remarkably, even the intra immunoglobulin gene deletions at 2p11 and 22q11 were detected, demonstrating the power of combining the detection sensitivity of array comparative genomic hybridization (CGH) with the resolution of an overlapping whole genome tiling-set. These alterations not only coincided with previously described aberrations in MCL, but also defined 13 novel regions. Further characterization of such minimally altered genomic regions identified using whole genome array CGH will define novel dominant oncogenes and tumor suppressor genes that play important roles in the pathogenesis of MCL.
* To whom correspondence should be addressed at: British Columbia Research Centre, 601 W. 10th Avenue, Vancouver, BC, Canada V5Z 1L3. Tel: +1 6048776000; Fax: +1 6048776155; Email: rdeleeuw{at}bccrc.ca
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