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Genome Biol. 2008;9(3):R59. doi: 10.1186/gb-2008-9-3-r59. Epub 2008 Mar 25.

A sequence-based survey of the complex structural organization of tumor genomes.

Author information

  • 1Department of Computer Science & Center for Computational Molecular Biology, Brown University, Waterman Street, Providence, RI 02912-1910, USA. braphael@brown.edu

Abstract

BACKGROUND:

The genomes of many epithelial tumors exhibit extensive chromosomal rearrangements. All classes of genome rearrangements can be identified using end sequencing profiling, which relies on paired-end sequencing of cloned tumor genomes.

RESULTS:

In the present study brain, breast, ovary, and prostate tumors, along with three breast cancer cell lines, were surveyed using end sequencing profiling, yielding the largest available collection of sequence-ready tumor genome breakpoints and providing evidence that some rearrangements may be recurrent. Sequencing and fluorescence in situ hybridization confirmed translocations and complex tumor genome structures that include co-amplification and packaging of disparate genomic loci with associated molecular heterogeneity. Comparison of the tumor genomes suggests recurrent rearrangements. Some are likely to be novel structural polymorphisms, whereas others may be bona fide somatic rearrangements. A recurrent fusion transcript in breast tumors and a constitutional fusion transcript resulting from a segmental duplication were identified. Analysis of end sequences for single nucleotide polymorphisms revealed candidate somatic mutations and an elevated rate of novel single nucleotide polymorphisms in an ovarian tumor.

CONCLUSION:

These results suggest that the genomes of many epithelial tumors may be far more dynamic and complex than was previously appreciated and that genomic fusions, including fusion transcripts and proteins, may be common, possibly yielding tumor-specific biomarkers and therapeutic targets.

PMID:
18364049
[PubMed - indexed for MEDLINE]
PMCID:
PMC2397511
Free PMC Article

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