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 FISHcalled 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 lowlevel 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. Chronic lymphocytic leukemia (CLL) is characterized by peripheral blood and bone marrow involvement by mature, monoclonal B-cells that co-express CD19, CD5, and CD23.1 CLL shows a variable clinical course that is correlated with phenotypic variability in a number of tumorassociated biomarkers, including serum lactate dehydrogenase, CD38 and ZAP70 expression, the degree of somatic mutation in the immunoglobulin heavy chain variable region genes, and specific genetic aberrations.
2-18The Rai and Binet staging systems, which are based on the extent of disease, remain among the most widely used predictors of prognosis. However, these predictors fail to identify those patients diagnosed with early stage disease who will have an aggressive clinical course.
19,20With the recent development of more effective and potentially curative regimens for CLL, a panel of tumorassociated biomarkers is increasingly performed during the initial workup of newly diagnosed patients and used to guide treatment. The detection of specific genomic alterations in CLL has emerged as one of the most important biomarker studies. Tumor-associated deletions of the short arm of chromosome (chr) 17 (del17p), seen in 5% to 10% of cases, and within the long arm of chr 11 involving bands q22-q24 (del11q 22.3), seen in 15% to 25% of cases, have been shown to be independent predictors of survival and disease progression in CLL. 10,18,21 In addition, the deletion of a small region at chr 13q14 and the presence of trisomy 12 have been shown to be of value in disease classification ...