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Arthur R. Brothman

Professor of Pediatrics and of Human Genetics

B.S. University of Arizona

Ph.D. University of Arizona

Research

References

art.brothman@genetics.utah.edu

 

Research

My laboratory focuses on the cytogenetic and molecular aspects of human prostatic cancer. Prostate cancer is the leading malignancy among U.S. males, with greater than 300,000 new cases diagnosed annually. Many of the men diagnosed with prostate cancer undergo radical surgery for treatment, yet there are no cellular markers to determine which tumors will be aggressive compared with other tumors that may not be life-threatening. One of the goals of my group is to identify genetic markers that can be predictive of clinical outcome. Recent advances have allowed us to begin understanding some of the basic genetic abnormalities associated with prostate tumor epithelial cells. Our methodologies involve cell culturing systems and chromosome preparation. We use conventional cytogenetics, fluorescence in situ hybridization (FISH) using chromosome-specific DNA probes, and genomic microarrays as tools for analysis. We also prepare nuclei from archival specimens to determine potential genetic changes in clinical cases in which there are now follow-up data.

Another focus is understanding the functional importance of any genes that appear to be altered in prostate tumors. Since we can grow cells in vitro, we can establish model systems to test how prostate tumor cells may respond to the addition (or removal) of DNA sequences that contain potentially important genes involved in the prostate carcinogenesis pathway. Our work involves collaborations with other basic science groups in addition to strong interactions with many of the clinicians involved in the treatment and diagnosis of prostate cancer.

Since I am part of the Division of Medical Genetics in the Department of Pediatrics, and run the diagnostic chromosome laboratory, my research group closely interacts with an applied testing environment. This allows for the implementation of new techniques (in both laboratories) and provides for stimulating projects relating to unusual clinical genetics cases that we may see.

 

A portion of a genomic microarray ratio plot from a prostate cancer patient showing copy number changes along chromosome 8.   BAC clones on the chip used are spaced at approximately 1 Mb intervals throughout the human genome and are depicted along the X axis of this plot.   This represents a double experiment with fluorescence dyes reversed, so separation of color signals indicates an abnormality.   This plot shows gain of multiple clones on the long arm of chromosome 8 (blue line above red line) and loss of clones on the short arm of chromosome 8 (red line above blue line).   The point where the lines switch is at the centromere of chromosome 8.

References