Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Genome Res. 2006 Mar;16(3):394-404. Epub 2006 Feb 3.

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

Author information

  • 1Department of Urology, and Cancer Research Institute, University of California San Francisco Comprehensive Cancer Center, San Francisco, California 94115, USA.

Abstract

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 co-amplification 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 anti-apoptotic 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.

PMID:
16461635
[PubMed - indexed for MEDLINE]
PMCID:
PMC1415204
Free PMC Article

Images from this publication.See all images (3)Free text

Figure 1.
Figure 2.
Figure 3.

Publication Types, MeSH Terms, Secondary Source ID, Grant Support

Publication Types

MeSH Terms

Secondary Source ID

Grant Support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk