In 2008, prostate cancer was the most prevalent cancer in men in the United States with 186,320 estimated new cases and 28,660 deaths. When detected early, prostate cancer can be curable, but procedures that offer the best prognosis such as radical prostatectomy - the complete removal of the prostate gland - often result in severe side. Clinical measures of metastatic potential of a localized prostate tumor often result in overly aggressive treatment. The goals of this research were to: (1) provide clinicians diagnostic markers with strong predictive power, (2) to reveal the mechanisms behind metastatic potential, and (3) identify targets for preventative and disease treatment. An integrated analysis combining data from genomic DNA copy number, gene expression and genome wide association was performed. We utilized the principles of evolutionary selection to build a model comparing the primary cancers of African American men and Caucasian American men with those of metastases which allowed us to delineate genes that select for metastatic potential versus those that oppose it. Results from this study suggest that a racial disparity exists, reflected in the somatic tumor genomes of African American and Caucasian American men. This genomic racial disparity involves putative prostate cancer candidate genes such as PTEN/PREX2a, AR and ERCC1 along with several novel candidates such as VASP and NME4. A comprehensive analysis in the context of putative protein interactions and gene sets revealed an enrichment for gene ontologies involved in cell adhesion, proliferation and cytoskeleton formation. Overall, the results imply that racial disparity for metastatic disease is driven by a variety of genes, each with variable selective influence over the function of three interconnected pathways controlling cellular structure and growth.
Some files may require a special program or browser plug-in. More Information
|Commitee:||Klueger, Yuval, Mishra, Bud, Schlick, Tamar, Schneider, Robert, Shao, Yongzhao|
|School:||New York University|
|School Location:||United States -- New York|
|Source:||DAI-B 70/12, Dissertation Abstracts International|
|Subjects:||Genetics, Bioinformatics, Oncology|
|Keywords:||Copy number, Genomic instability, Health disparities, Metastasis, Prostate cancer|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be