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

Benjamin J Raphael1, Stanislav Volik2, Peng Yu3, Chunxiao Wu4, Guiqing Huang2, Elena V Linardopoulou5, Barbara J Trask5, Frederic Waldman2, Joseph Costello2, Kenneth J Pienta6, Gordon B Mills7, Krystyna Bajsarowicz2, Yasuko Kobayashi2, Shivaranjani Sridharan2, Pamela L Paris2, Quanzhou Tao8, Sarah J Aerni9, Raymond P Brown10, Ali Bashir10, Joe W Gray11, Jan-Fang Cheng12, Pieter de Jong13, Mikhail Nefedov13, Thomas Ried14, Hesed M Padilla-Nash14 and Colin C Collins2*

Author Affiliations

1 Department of Computer Science & Center for Computational Molecular Biology, Brown University, Waterman Street, Providence, RI 02912-1910, USA

2 Cancer Research Institute, UCSF Comprehensive Cancer Center, Sutter Street, San Francisco, CA 94115, USA

3 Chinese National Human Genome Center, North Yongchang Road, BDA, Beijing, P.R.C. 100016

4 Shandong Provincial Hospital, JingWuWeiQi Road, Jinan, P.R.C. 250021

5 Division of Human Biology, Fred Hutchinson Cancer Research Center, Fairview Avenue N, Seattle, WA 98109, USA

6 The University of Michigan, Departments of Internal Medicine and Urology, E Medical Center Drive, Ann Arbor, MI 48109-0330, USA

7 MD Anderson Cancer Center, University of Texas, Holcombe Blvd, Houston, TX 77030, USA

8 Amplicon Express, NE Eastgate Blvd, Pullman, WA 99163, USA

9 BioMedical Informatics Program, Stanford University, Stanford, CA 94305, USA

10 Bioinformatics Program, University of California, San Diego, Gilman Drive, La Jolla, CA 92093, USA

11 Lawrence Berkeley National Laboratory, Life Sciences Division, Cyclotron Road, Berkeley, CA 94720-8268, USA

12 Lawrence Berkeley National Laboratory, Genomics Division and Joint Genome Institute, Cyclotron Road, Berkeley, CA 94720, USA

13 BACPAC Resources Children's Hospital Oakland, 52nd Street, Oakland, CA 94609, USA

14 Section of Cancer Genomics, Genetics Branch, Center for Cancer Research, South Drive, Bldg. 50, MSC-8010, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

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Genome Biology 2008, 9:R59  doi:10.1186/gb-2008-9-3-r59

Published: 25 March 2008



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.


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.


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.