Whole-Genome Scanning by Array Comparative Genomic Hybridization as a Clinical Tool for Risk Assessment in Chronic Lymphocytic Leukemia

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Journal of Molecular Diagnostics, doi:10.2353/jmoldx.2008.080033

Whole-Genome Scanning by Array Comparative Genomic Hybridization as a Clinical

Tool for Risk Assessment in Chronic Lymphocytic Leukemia

R. Gunn*@, Mansoor S. Mohammed, Mercedes E. Gorre, Philip D. Cotter,

Jaeweon Kim, W. Bahler, Sergey N. Preobrazhensky, A. Higgins*,

Aswani R. Bolla*, Sahar H. Ismail*, Daphne de Jong, Eldering¶, Marinus H.J.

van Oers||, Clemens H.M. Mellink**, J. Keating, Ellen J. Schlette, Lynne

V. Abruzzo, and S. Robetorye*

From the Department of Pathology,* The University of Texas Health Science Center

at San , San , Texas; the Departments of Leukemia and

Hematopathology, University of Texas M.D. Cancer Center, Houston,

Texas; Combimatrix Molecular Diagnostics Incorporated, Irvine, California; the

Department of Pathology and ARUP Institute for Clinical and Experimental

Pathology, University of Utah, Salt Lake City, Utah; the Department of

Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; and the

Departments of Experimental Immunology,¶ Hematology,|| and Clinical Genetics,**

Academic Medical Center, Amsterdam, The Netherlands

@ To whom correspondence should be addressed. E-mail: gunn@... .

Abstract

Array-based comparative genomic hybridization (array CGH) provides a powerful

method for simultaneous genome-wide scanning and prognostic marker assessment in

chronic lymphocytic leukemia (CLL). In the current study, commercially available

bacterial artificial chromosome and oligonucleotide array CGH platforms were

used to identify chromosomal alterations of prognostic significance in 174 CLL

cases. Tumor genomes were initially analyzed by bacterial artificial chromosome

array CGH followed by confirmation and breakpoint mapping using oligonucleotide

arrays. Genomic changes involving loci currently interrogated by fluorescence in

situ hybridization (FISH) panels were detected in 155 cases (89%) at expected

frequencies: 13q14 loss (47%), trisomy 12 (13%), 11q loss (11%), 6q loss (7.5%),

and 17p loss (4.6%). Genomic instability was the second most commonly identified

alteration of prognostic significance with three or more alterations involving

loci not interrogated by FISH panels identified in 37 CLL cases (21%). A subset

of 48 CLL cases analyzed by six-probe FISH panels (288 total hybridizations) was

concordant with array CGH results for 275 hybridizations (95.5%); 13

hybridizations (4.5%) were discordant because of clonal populations that

comprised less than 30% of the sample. Array CGH is a powerful, cost-effective

tool for genome-wide risk assessment in the clinical evaluation of CLL.