title: Customized oligonucleotide array-based comparative genomic hybridization as a clinical assay for genomic profiling of chronic lymphocytic leukemia.
abstract: 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.
authors.affiliation: Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Rachel
authors.initials: R
authors.lastname: Sargent
authors.affiliation: Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.affiliation: Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Lynne V
authors.initials: LV
authors.lastname: Abruzzo
authors.affiliation: Division of Quantitative Sciences, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Hui
authors.initials: H
authors.lastname: Yao
authors.affiliation: Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Jaime
authors.initials: J
authors.lastname: Bonderover
authors.affiliation: Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Marissa
authors.initials: M
authors.lastname: Cisneros
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: William G
authors.initials: WG
authors.lastname: Wierda
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
authors.affiliation: Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. Electronic address: rluthra@mdanderson.org.
authors.forename: Rajyalakshmi
authors.initials: R
authors.lastname: Luthra
mesh_terms: 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