Decoding the fine-scale structure of a breast cancer genome and transcriptome

Stanislav Volik, Benjamin J. Raphael, Guiqing Huang, Michael R. Stratton, Graham Bignel, John Murnane, John H. Brebner, Krystyna Bajsarowicz, Pamela L. Paris, Quanzhou Tao, David Kowbel, Anna Lapuk, Dmitri A. Shagin, Irina A. Shagina, Joe W. Gray, Jan Fang Cheng, Pieter J. De Jong, Pavel Pevzner, Colin Collins

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


A comprehensive understanding of cancer is predicated upon knowledge of the structure of malignant genomes underlying its many variant forms and the molecular mechanisms giving rise to them. It is well established that solid tumor genomes accumulate a large number of genome rearrangements during tumorigenesis. End Sequence Profiling (ESP) maps and clones genome breakpoints associated with all types of genome rearrangements elucidating the structural organization of tumor genomes. Here we extend the ESP methodology in several directions using the breast cancer cell line MCF-7. First, targeted ESP is applied to multiple amplified loci, revealing a complex process of rearrangement and coamplification in these regions reminiscent of breakage/fusion/bridge cycles. Second, genome breakpoints identified by ESP are confirmed using a combination of DNA sequencing and PCR. Third, in vitro functional studies assign biological function to a rearranged tumor BAC clone, demonstrating that it encodes antiapoptotic activity. Finally, ESP is extended to the transcriptome identifying four novel fusion transcripts and providing evidence that expression of fusion genes may be common in tumors. These results demonstrate the distinct advantages of ESP including: (1) the ability to detect all types of rearrangements and copy number changes; (2) straightforward integration of ESP data with the annotated genome sequence; (3) immortalization of the genome; (4) ability to generate tumor-specific reagents for in vitro and in vivo functional studies. Given these properties, ESP could play an important role in a tumor genome project.

Original languageEnglish (US)
Pages (from-to)394-404
Number of pages11
JournalGenome Research
Issue number3
StatePublished - Mar 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)
  • Genetics


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