Customized oligonucleotide array-based comparative genomic hybridization as a clinical assay for genomic profiling of chronic lymphocytic leukemia.
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.
Sargent
Rachel
R
Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
Jones
Dan
D
Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
Abruzzo
Lynne V
LV
Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
Yao
Hui
H
Division of Quantitative Sciences, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
Bonderover
Jaime
J
Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
Cisneros
Marissa
M
Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
Wierda
William G
WG
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
Keating
Michael J
MJ
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
Luthra
Rajyalakshmi
R
Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. Electronic address: rluthra@mdanderson.org.
D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D055028:Comparative Genomic Hybridization / Q000379:methods*; D020869:Gene Expression Profiling / Q000379:methods; D015894:Genome, Human; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012680:Sensitivity and Specificity