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Am J Hematol. 2008 Jul;83(7):540-6.

Validation of a targeted DNA microarray for the clinical evaluation of recurrent abnormalities in chronic lymphocytic leukemia.

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Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77024, USA.


Recurrent genomic alterations, mainly losses and gains of specific chromosomes and/or regions, in chronic lymphocytic leukemia (CLL) are recognized as important independent predictors of prognosis and disease progression. The current standard clinical practice for identifying these alterations is chromosome analysis and in situ hybridization with probes targeting 4-5 chromosome regions. We sought to apply array comparative genomic hybridization (array-CGH) technology for the simultaneous detection of genomic imbalances of all loci implicated in CLL. DNA from enriched B-cells from CLL patients were analyzed by array-CGH on a customized CLL BAC array. Copy number changes were detected in 87% of samples with a sensitivity of 100% in samples with clonal abnormalities present in at least 23% of the cells. Furthermore, in nine cases genomic alterations were observed that were undetectable by standard cytogenetic and/or FISH analyses. One of these patients had a 13q14 deletion that was missed by the clinical CLL FISH panel probe set. Our results suggest that a subset of potentially significant genomic alterations in CLL is being missed by the current available techniques. Furthermore, this pilot study clearly shows the robustness, high sensitivity, and high specificity for the targeted CLL microarray analysis as well as the potential for use in routine screening in CLL.

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