The general aim of the present application is to recruit newly available genomic technologies such as Bacterial Artificial Chromosome (BAC) library preparations, finished sequence of the human genome, and next- generation sequencing technologies developed by the 454 Life Sciences Corporation in the fight against cancer. This application aims to develop the Barcoded Tag Pooled Genomic Indexing (BT-PGI) method for highly multiplexed BAC-based mapping of chromosomal aberrations in cancer. The BT-PGI method achieves throughput and resolution by combining two types of multiplexing -- the pooling of BAC clones by the PGI method and the parallel sequencing of short mappable sequence tags by the newly developed 454 sequencing technology. A commercially available BAC library obtained from the well-established MCF-7 breast cancer cell line will be used for'testing and validation of these methods. Specific rearrangements detected in MCF-7 will then be measured in other breast cancer cell lines, and in breast cancer tissue. The biological function of these rearrangements will be tested by cloning and expression in both immortalized and transformed breast epithelial cells. Biological assays will depend upon the rearrangement or breakpoints of interest, but will focus on proliferation, survival, invasion and transformation. The improved understanding of chromosomal rearrangements will open new opportunities for charting the progression of cancer, understanding relevant molecular mechanisms, identifying biomarkers for informed therapy, and identifying targets for therapeutic intervention in breast cancer and other tumors. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
5R33CA114151-02
Application #
7414737
Study Section
Special Emphasis Panel (ZCA1-SRRB-K (O1))
Program Officer
Li, Jerry
Project Start
2007-05-01
Project End
2010-04-30
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
2
Fiscal Year
2008
Total Cost
$229,170
Indirect Cost
Name
Baylor College of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
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Miller, Christopher A; Settle, Stephen H; Sulman, Erik P et al. (2011) Discovering functional modules by identifying recurrent and mutually exclusive mutational patterns in tumors. BMC Med Genomics 4:34
Miller, Christopher A; Hampton, Oliver; Coarfa, Cristian et al. (2011) ReadDepth: a parallel R package for detecting copy number alterations from short sequencing reads. PLoS One 6:e16327
Hampton, Oliver A; Den Hollander, Petra; Miller, Christopher A et al. (2009) A sequence-level map of chromosomal breakpoints in the MCF-7 breast cancer cell line yields insights into the evolution of a cancer genome. Genome Res 19:167-77
Coarfa, Cristian; Milosavljevic, Aleksandar (2008) Pash 2.0: scaleable sequence anchoring for next-generation sequencing technologies. Pac Symp Biocomput :102-13