RT Journal
A1 Volik, Stanislav
A1 Raphael, Benjamin J.
A1 Huang, Guiqing
A1 Stratton, Michael R.
A1 Bignel, Graham
A1 Murnane, John
A1 Brebner, John H.
A1 Bajsarowicz, Krystyna
A1 Paris, Pamela L.
A1 Tao, Quanzhou
A1 Kowbel, David
A1 Lapuk, Anna
A1 Shagin, Dmitri A.
A1 Shagina, Irina A.
A1 Gray, Joe W.
A1 Cheng, Jan-Fang
A1 de Jong, Pieter J.
A1 Pevzner, Pavel
A1 Collins, Colin
T1 Decoding the fine-scale structure of a breast cancer genome and transcriptome
JF Genome Research 
JO Genome Research 
YR 2006 
FD March 01 
VO 16 
IS 3 
SP 394 
OP 404 
DO 10.1101/gr.4247306 
UL http://genome.cshlp.org/content/16/3/394.abstract 
AB 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.