PMID- 19074592 OWN - NLM STAT- MEDLINE DCOM- 20090505 LR - 20211020 IS - 1525-1578 (Print) IS - 1943-7811 (Electronic) IS - 1525-1578 (Linking) VI - 11 IP - 1 DP - 2009 Jan TI - Customized oligonucleotide array-based comparative genomic hybridization as a clinical assay for genomic profiling of chronic lymphocytic leukemia. PG - 25-34 LID - S1525-1578(10)60205-X [pii] LID - 10.2353/jmoldx.2009.080037 [doi] AB - 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. FAU - Sargent, Rachel AU - Sargent R AD - Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. FAU - Jones, Dan AU - Jones D AD - Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. FAU - Abruzzo, Lynne V AU - Abruzzo LV AD - Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. FAU - Yao, Hui AU - Yao H AD - Division of Quantitative Sciences, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. FAU - Bonderover, Jaime AU - Bonderover J AD - Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. FAU - Cisneros, Marissa AU - Cisneros M AD - Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. FAU - Wierda, William G AU - Wierda WG AD - Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. FAU - Keating, Michael J AU - Keating MJ AD - Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. FAU - Luthra, Rajyalakshmi AU - Luthra R AD - Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. Electronic address: rluthra@mdanderson.org. LA - eng GR - P30 CA016672/CA/NCI NIH HHS/United States GR - CA16672/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20081212 PL - United States TA - J Mol Diagn JT - The Journal of molecular diagnostics : JMD JID - 100893612 SB - IM MH - Chromosomes, Human, Pair 12/genetics MH - Comparative Genomic Hybridization/*methods MH - Gene Expression Profiling/methods MH - Genome, Human MH - Humans MH - Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis/*genetics MH - Oligonucleotide Array Sequence Analysis/*methods MH - Sensitivity and Specificity PMC - PMC2607562 EDAT- 2008/12/17 09:00 MHDA- 2009/05/06 09:00 PMCR- 2010/01/01 CRDT- 2008/12/17 09:00 PHST- 2008/12/17 09:00 [entrez] PHST- 2008/12/17 09:00 [pubmed] PHST- 2009/05/06 09:00 [medline] PHST- 2010/01/01 00:00 [pmc-release] AID - S1525-1578(10)60205-X [pii] AID - JMDI60205 [pii] AID - 10.2353/jmoldx.2009.080037 [doi] PST - ppublish SO - J Mol Diagn. 2009 Jan;11(1):25-34. doi: 10.2353/jmoldx.2009.080037. Epub 2008 Dec 12.