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A sequence-based survey of the complex structural organization of tumor genomes
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, an...
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BioMed Central
2008
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| Acesso em linha: | https://ncbi.nlm.nih.gov/pmc/articles/PMC2397511/ https://ncbi.nlm.nih.gov/pubmed/18364049 https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1186/gb-2008-9-3-r59 |
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pubmed-23975112008-05-30 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 B Bajsarowicz, Krystyna Kobayashi, Yasuko Sridharan, Shivaranjani Paris, Pamela L Tao, Quanzhou Aerni, Sarah J Brown, Raymond P Bashir, Ali Gray, Joe W Cheng, Jan-Fang de Jong, Pieter Nefedov, Mikhail Ried, Thomas Padilla-Nash, Hesed M Collins, Colin C Genome Biol Research 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. BioMed Central 2008 2008-03-25 /pmc/articles/PMC2397511/ /pubmed/18364049 http://dx.doi.org/10.1186/gb-2008-9-3-r59 Text en Copyright © 2008 Raphael et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| institution |
US National Library of Medicine |
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PubMed Central |
| language |
English |
| format |
Article |
| topic |
Research |
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Research 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 B Bajsarowicz, Krystyna Kobayashi, Yasuko Sridharan, Shivaranjani Paris, Pamela L Tao, Quanzhou Aerni, Sarah J Brown, Raymond P Bashir, Ali Gray, Joe W 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 |
| description |
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. |
| author |
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 B Bajsarowicz, Krystyna Kobayashi, Yasuko Sridharan, Shivaranjani Paris, Pamela L Tao, Quanzhou Aerni, Sarah J Brown, Raymond P Bashir, Ali Gray, Joe W Cheng, Jan-Fang de Jong, Pieter Nefedov, Mikhail Ried, Thomas Padilla-Nash, Hesed M Collins, Colin C |
| author_facet |
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 B Bajsarowicz, Krystyna Kobayashi, Yasuko Sridharan, Shivaranjani Paris, Pamela L Tao, Quanzhou Aerni, Sarah J Brown, Raymond P Bashir, Ali Gray, Joe W Cheng, Jan-Fang de Jong, Pieter Nefedov, Mikhail Ried, Thomas Padilla-Nash, Hesed M Collins, Colin C |
| author_sort |
Raphael, Benjamin J |
| title |
A sequence-based survey of the complex structural organization of tumor genomes |
| title_short |
A sequence-based survey of the complex structural organization of tumor genomes |
| title_full |
A sequence-based survey of the complex structural organization of tumor genomes |
| title_fullStr |
A sequence-based survey of the complex structural organization of tumor genomes |
| title_full_unstemmed |
A sequence-based survey of the complex structural organization of tumor genomes |
| title_sort |
sequence-based survey of the complex structural organization of tumor genomes |
| publisher |
BioMed Central |
| publisher_facet |
BioMed Central |
| publishDate |
2008 |
| url |
https://ncbi.nlm.nih.gov/pmc/articles/PMC2397511/ https://ncbi.nlm.nih.gov/pubmed/18364049 https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1186/gb-2008-9-3-r59 |
| _version_ |
1760584706375548928 |