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Rapid High-Resolution Mapping of Balanced Chromosomal Rearrangements on Tiling CGH Arrays

https://doi.org/10.1016/j.jmoldx.2011.07.005Get rights and content
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The diagnosis and classification of many cancers depends in part on the identification of large-scale genomic aberrations such as chromosomal deletions, duplications, and balanced translocations. Array-based comparative genomic hybridization (array CGH) can detect chromosomal imbalances on a genome-wide scale but cannot reliably identify balanced chromosomal rearrangements. We describe a simple modification of array CGH that enables simultaneous identification of recurrent balanced rearrangements and genomic imbalances on the same microarray. Using custom tiling oligonucleotide arrays and gene-specific linear amplification primers, translocation CGH (tCGH) maps balanced rearrangements to ∼100-base resolution and facilitates the rapid cloning and sequencing of novel rearrangement breakpoints. As proof of principle, we used tCGH to characterize nine of the most common gene fusions in mature B-cell neoplasms and myeloid leukemias. Because tCGH can be performed in any CGH-capable laboratory and can screen for multiple recurrent translocations and genome-wide imbalances, it should be of broad utility in the diagnosis and classification of various types of lymphomas, leukemias, and solid tumors.

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Supported in part by a pilot grant from the Fred Hutchinson/University of Washington Cancer Consortium Cancer Center support grant (NIH-NCI grant 5-P30-CA015704) and by research support from Agilent Technologies Foundation (H.A.G.).

H.A.G. has filed a patent application for the method described in this article, and the University of Washington has licensed this technology to Signature Genomics, LLC, of Spokane, WA. All three authors have received royalties/licensing fees from Signature Genomics related to this license. H.A.G. also has received microarray reagents from Agilent Technologies.

Supplemental material for this article can be found at http://jmd.amjpathol.org or at doi: 10.1016/j.jmoldx.2011.07.005.