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Analysis of Chromothripsis by Combined FISH and Microarray Analysis.

Fluorescence in situ hybridization (FISH) to metaphase chromosomes, in conjunction with SNP array, array CGH, or whole genome sequencing, can help determine the organization of abnormal genomes after chromothripsis and other types of complex genome rearrangement. DNA microarrays can identify the changes in copy number, but they do not give information on the organization of the abnormal chromosomes, balanced rearrangements, or abnormalities of the centromeres and other regions comprised of highly repetitive DNA. Many of these details can be determined by the strategic use of metaphase FISH. FISH is a single-cell technique, so it can identify low-frequency chromosome abnormalities, and it can determine which chromosome abnormalities occur in the same or different clonal populations. These are important considerations in cancer. Metaphase chromosomes are intact, so information about abnormalities of the chromosome homologues is preserved. Here we describe strategies for working out the organization of highly rearranged genomes by combining SNP array data with various metaphase FISH methods. This approach can also be used to address some of the uncertainties arising from whole genome or mate-pair sequencing data.

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