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Originally published online as doi:10.2353/jmoldx.2009.080037 on December 12, 2008

Published online before print December 12, 2008
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Journal of Molecular Diagnostics 2009, Vol. 11, No. 1
Copyright © 2009 American Society for Investigative Pathology & Association for Molecular Pathology
DOI: 10.2353/jmoldx.2009.080037

Customized Oligonucleotide Array-Based Comparative Genomic Hybridization as a Clinical Assay for Genomic Profiling of Chronic Lymphocytic Leukemia

Rachel Sargent*, Dan Jones*, Lynne V. Abruzzo*, Hui Yao{dagger}, Jaime Bonderover*, Marissa Cisneros*, William G. Wierda{ddagger}, Michael J. Keating{ddagger} and Rajyalakshmi Luthra*

From the Department of Hematopathology, * the Division of Quantitative Sciences, {dagger} and the Department of Leukemia, {ddagger} The University of Texas M. D. Anderson Cancer Center, Houston, Texas

Chromosome gains and losses used for risk stratification in chronic lymphocytic leukemia (CLL) are commonly assessed by multiprobe fluorescence in situ hybridization (FISH) studies. We designed and validated a customized array-comparative genomic hybridization (aCGH) platform as a clinical assay for CLL genomic profiling. A 60-mer, 44,000-probe oligonucleotide array with a 50-kb average spatial resolution was augmented with high-density probe tiling at loci that are frequently aberrant in CLL. Aberrations identified by aCGH were compared with those identified by a FISH panel, including locus-specific probes to ATM (11q22.3), the centromeric region of chromosome 12 (12p11.1–q11), D13S319 (13q14.3), LAMP1 (13q34), and TP53 (17p13.1). In 100 CLL samples, aCGH/FISH concordance was seen for 89% of FISH-called aberrations at the ATM (n = 18), D13S319 (n = 42), LAMP (n = 12), and TP53 (n = 22) loci and for chromosome 12 (n = 14). Eighty-four percentage of FISH/aCGH discordant calls were in samples either at or below the limit of aCGH sensitivity (10% to 25% FISH aberration-containing cells). Therefore, aCGH profiling is a feasible routine clinical test with comparable results to multiprobe FISH studies; however, it may be less sensitive than FISH in cases with low-level aberrations. Further, a customized array design can provide comprehensive genomic profiling with additional accuracy in both identifying and defining the extent of small aberrations at target loci.







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Copyright © 2009 by the American Society for Investigative Pathology and the Association for Molecular Pathology.