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

Benjamin J. Raphael, Stanislav Volik, Peng Yu, Chunxiao Wu, Guiqing Huang, Elena V. Linardopoulou, Barbara J. Trask, Frederic Waldman, Joseph Costello, Kenneth J. Pienta, Gordon Mills, Krystyna Bajsarowicz, Yasuko Kobayashi, Shivaranjani Sridharan, Pamela L. Paris, Quanzhou Tao, Sarah J. Aerni, Raymond P. Brown, Ali Bashir, Joe GrayJan Fang Cheng, Pieter de Jong, Mikhail Nefedov, Thomas Ried, Hesed M. Padilla-Nash, Colin C. Collins

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish (US)
Article numberR59
JournalGenome Biology
Volume9
Issue number3
DOIs
StatePublished - Mar 25 2008
Externally publishedYes

Fingerprint

tumor
genome
Genome
neoplasms
Neoplasms
breast neoplasms
single nucleotide polymorphism
polymorphism
Single Nucleotide Polymorphism
genomics
Genomic Segmental Duplications
somatic mutation
Breast Neoplasms
ovarian neoplasms
prostatic neoplasms
fluorescence in situ hybridization
Surveys and Questionnaires
Product Packaging
Mutation Rate
packaging

ASJC Scopus subject areas

  • Genetics
  • Cell Biology
  • Ecology, Evolution, Behavior and Systematics

Cite this

Raphael, B. J., Volik, S., Yu, P., Wu, C., Huang, G., Linardopoulou, E. V., ... Collins, C. C. (2008). A sequence-based survey of the complex structural organization of tumor genomes. Genome Biology, 9(3), [R59]. https://doi.org/10.1186/gb-2008-9-3-r59

A sequence-based survey of the complex structural organization of tumor genomes. / Raphael, Benjamin J.; Volik, Stanislav; Yu, Peng; Wu, Chunxiao; Huang, Guiqing; Linardopoulou, Elena V.; Trask, Barbara J.; Waldman, Frederic; Costello, Joseph; Pienta, Kenneth J.; Mills, Gordon; Bajsarowicz, Krystyna; Kobayashi, Yasuko; Sridharan, Shivaranjani; Paris, Pamela L.; Tao, Quanzhou; Aerni, Sarah J.; Brown, Raymond P.; Bashir, Ali; Gray, Joe; Cheng, Jan Fang; de Jong, Pieter; Nefedov, Mikhail; Ried, Thomas; Padilla-Nash, Hesed M.; Collins, Colin C.

In: Genome Biology, Vol. 9, No. 3, R59, 25.03.2008.

Research output: Contribution to journalArticle

Raphael, BJ, Volik, S, Yu, P, Wu, C, Huang, G, Linardopoulou, EV, Trask, BJ, Waldman, F, Costello, J, Pienta, KJ, Mills, G, Bajsarowicz, K, Kobayashi, Y, Sridharan, S, Paris, PL, Tao, Q, Aerni, SJ, Brown, RP, Bashir, A, Gray, J, Cheng, JF, de Jong, P, Nefedov, M, Ried, T, Padilla-Nash, HM & Collins, CC 2008, 'A sequence-based survey of the complex structural organization of tumor genomes', Genome Biology, vol. 9, no. 3, R59. https://doi.org/10.1186/gb-2008-9-3-r59
Raphael BJ, Volik S, Yu P, Wu C, Huang G, Linardopoulou EV et al. A sequence-based survey of the complex structural organization of tumor genomes. Genome Biology. 2008 Mar 25;9(3). R59. https://doi.org/10.1186/gb-2008-9-3-r59
Raphael, Benjamin J. ; Volik, Stanislav ; Yu, Peng ; Wu, Chunxiao ; Huang, Guiqing ; Linardopoulou, Elena V. ; Trask, Barbara J. ; Waldman, Frederic ; Costello, Joseph ; Pienta, Kenneth J. ; Mills, Gordon ; Bajsarowicz, Krystyna ; Kobayashi, Yasuko ; Sridharan, Shivaranjani ; Paris, Pamela L. ; Tao, Quanzhou ; Aerni, Sarah J. ; Brown, Raymond P. ; Bashir, Ali ; Gray, Joe ; Cheng, Jan Fang ; de Jong, Pieter ; Nefedov, Mikhail ; Ried, Thomas ; Padilla-Nash, Hesed M. ; Collins, Colin C. / A sequence-based survey of the complex structural organization of tumor genomes. In: Genome Biology. 2008 ; Vol. 9, No. 3.
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AU - Gray, Joe

AU - Cheng, Jan Fang

AU - de Jong, Pieter

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N2 - 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.

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