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Dissertation/Thesis Abstract

Prostate cancer health disparity in African American and Caucasian American men characterized through the landscape of genomic instability
by Pearlman, Alexander, Ph.D., New York University, 2009, 91; 3380267
Abstract (Summary)

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.

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Indexing (document details)
Advisor: Ostrer, Harry
Commitee: Klueger, Yuval, Mishra, Bud, Schlick, Tamar, Schneider, Robert, Shao, Yongzhao
School: New York University
Department: Chemistry
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
Publication Number: 3380267
ISBN: 978-1-109-50663-1
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