Arthur R. Brothman
Professor of Pediatrics and of Human Genetics
B.S. University of Arizona
Ph.D. University of Arizona
art.brothman@genetics.utah.edu
Research
My laboratory has focused on the cytogenetic and molecular aspects of human prostatic cancer. Prostate cancer is the leading malignancy among U.S. males, with greater than 200,000 new cases diagnosed annually; it is the second leading cause of male cancer deaths. Many of the men diagnosed with prostate cancer undergo radical surgery for treatment, yet there are no reliable 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 research group has been 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 have involved conventional cytogenetics, fluorescence in situ hybridization (FISH) using chromosome-specific DNA probes, and comparative genomic hybridization microarrays as tools for analysis. 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.
I am a faculty member in the Division of Medical Genetics in the Department of Pediatrics, Laboratory Director of the CGH Microarray facility at the University and Medical Director of Cytogenetics at A.R.U.P . These positions have allowed for close interaction between the research and diagnostic labs in an applied testing environment. This facilitates 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 CGH microarray ratio plot from a prostate cancer patient showing copy number changes along chromosome 3. Deviations from the “0” point represent losses of this region of the chromosome when tumor DNA is compared with a normal control, The microarray platform used has approximately 244,000 oliognucleotides spanning the human genome sequences.
References
1. Aston E, Whitby H, Maxwell T, Glaus N, Cowley B, Lowry D, Zhu Xiao Lin, Issa B, South ST, Brothman AR (2008) Comparison of targeted and whole genome analysis of postnatal specimens using a commercially available aCGH Microarray platform. J Med Genet 45:268-274
2. South ST, Whitby H, Battaglia A, Carey JC, Brothman AR (2008) Comprehensive analysis of Wolf-Hirschhorn syndrome using array CGH indicates a high prevalence of translocations. Eur J Human Genet 16(1):45-52
3. Saam J, Gudgeon J, Aston E, Brothman AR (2008) How physicians use array comparative genomic hybridization results to guide patient management in children with developmental delay. Genetics in Medicine 10(3):181-6
4. Shaffer LG, Beaudet A, Brothman AR, Hirsch B, Levy B, Martin CL, Mascarello J, Rao KW (2007) Microarray Analysis for Constitutional Cytogenetic Abnormalities. Genet Med. 9(9):654-62
5. Lee AJ, Iafrate, Brothman AR (2007) Copy number variation (CNV) and clinical cytogenetic diagnostics. Nature Genetics 39(7):S49-S54
6. Svensson AM, Curry CJ, South ST, Whitby H, Maxwell TM, Aston E, Fisher J, Carmack C, Scheffer A, Abu-Shamsieh A, Brothman AR (2007) Detection of a De Novo Interstitial 2q Microdeletion by CGH Microarray Analysis in a Patient with Limb Malformations, Microcephaly and Mental Retardation. Am J Med Genet A 143(12):1348-53
7. Brothman AR, Swanson G, Maxwell TM, Cui J, Murphy KJ, Herrick J, Speights VO, Isaac J, Rohr LR (2005) Global hypomethylation is common in prostate cancer cells: a quantitative predictor for clinical outcome? Cancer Genetics and Cytogenetics 156:31-36
8. Pettus JA, Cowley BC, Maxwell T, Milash B, Stephenson RA, Rohr LR, Hoff C, Brothman AR (2004) Multiple abnormalities detected by dye reversal genomic microarrays in prostate cancer: a much greater sensitivity than conventional cytogenetics. Cancer Genetics and Cytogenetics 154:110-119
9. Stevenson DA, Carey JC, Cowley BC, Mao R, Bayrak-Toydemir P, Brothman AR (2004) 4p terminal deletion and 11p subtelomeric duplication detected by genomic microarray in a patient with Wolf-Hirschhorn Syndrome and an Atypical Phenotype. The Journal of Pediatrics 840-842
10. Brothman AR (2002) Cytogenetics and Molecular Genetics of Cancer of the Prostate, Seminars in Medical Genetics. Am. J. Med. Genetics (Seminars in Medical Genetics) 115:150-156
