The long-term objective of this project is to improve the detection of one of the common human cancers arising in the bladder by non-invasive voided urine-based tests. Bladder cancer is the 4"^ most frequent in men and 5"" most common overall with approximately 70,500 new cases and 14,600 deaths from the disease in 2009 in the United States. It is estimated that nearly 300,000 patients are regularly monitored in the United States through a vanety of non-invasive (urine) and minimally invasive (bladder barbotage, cystoscopy, and biopsy) techniques. Therefore, the development of novel biomarkers that can detect bladder tumors by a non-invasive approach is of major clinical significance. In this grant, we propose to complement the existing Multi-Institutional Aurora kinase A FISH Test Biomarker Validation Trial by novel FISH markers and explore the role of Aurora kinase A in bladder cancer progression. We will compare the specificity and sensitivity of aurora A FISH test complemented by a panel of novel FISH markers with other known noninvasive bladder cancer detection tests for voided urine sediments such as urine cytology and commercially available multi-chromosomal FISH kit known as UroVysion, and NMP22 point-of-care test. A panel of novel FISH markers will be developed by whole-organ histologic and genetic mapping (WOHGM) strategy combined with high resolution (IM) lllumina SNP-based genotyping, which provides unique information on the chronology of genomic alterations that parallel the development of bladder cancer from early field effects to invasive disease. Our strong preliminary data indicate that this approach offers a unique opportunity to design novel biomarkers that may address the specific phases of bladder cancer development along these superficial papillary and high grade nonpapillary Invasive pathways. Moreover, we propose to investigate the role of aurora kinase A and its regular pathway in bladder cancer progression to invasive disease and distant metastasis.
The specific aims of this project are as follows:
Specific Aim 1 : Develop a panel of novel FISH markers for bladder cancer.
Specific Aim 2 : Validate a novel set of FISH biomarkers for bladder cancer.
Specific Aim 3 : Investigate the role of Aurora kinase A in bladder cancer growth, angiogenesis, invasion and metastasis.

Public Health Relevance

In this grant we propose to develop and validate a novel set of FISH markers and compare it with aurora A FISH test as a biomarker for the detection of bladder cancer in the multi-institutional validation protocol. In this trial the performance of novel FISH tests will be compared with cytology, UroVysion FISH, and NMP22 tests. Given the high frequency of bladder cancer, the development of specific and sensitive tests for the disease by a non-Invasive approach will have a great impact on its management. The clinical use of such a test will represent a novel standard of practice facilitating early treatment of bladder cancer and positively affecting the survival rates of the patients with bladder cancer. The biomarker studies will be complemented by mechanistic studies focused on the role of aurora kinase A in bladder cancer progression including invasion, angiogenesis, and metastasis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
2P50CA091846-11
Application #
8230252
Study Section
Special Emphasis Panel (ZCA1-RPRB-M (O1))
Project Start
2011-09-01
Project End
2017-08-31
Budget Start
2012-09-19
Budget End
2012-08-31
Support Year
11
Fiscal Year
2012
Total Cost
$203,201
Indirect Cost
$66,291
Name
University of Texas MD Anderson Cancer Center
Department
Type
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
Dadhania, Vipulkumar; Zhang, Miao; Zhang, Li et al. (2016) Meta-Analysis of the Luminal and Basal Subtypes of Bladder Cancer and the Identification of Signature Immunohistochemical Markers for Clinical Use. EBioMedicine 12:105-117
von Rundstedt, Friedrich-Carl; Mata, Douglas A; Shen, Steven et al. (2016) Transurethral biopsy of the prostatic urethra is associated with final apical margin status at radical cystoprostatectomy. J Clin Urol 9:404-408
McConkey, David J; Choi, Woonyoung; Shen, Yu et al. (2016) A Prognostic Gene Expression Signature in the Molecular Classification of Chemotherapy-naïve Urothelial Cancer is Predictive of Clinical Outcomes from Neoadjuvant Chemotherapy: A Phase 2 Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cis Eur Urol 69:855-62
Kamat, Ashish M; Briggman, Joseph; Urbauer, Diana L et al. (2016) Cytokine Panel for Response to Intravesical Therapy (CyPRIT): Nomogram of Changes in Urinary Cytokine Levels Predicts Patient Response to Bacillus Calmette-Guérin. Eur Urol 69:197-200
Machiela, Mitchell J; Zhou, Weiyin; Karlins, Eric et al. (2016) Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome. Nat Commun 7:11843
Figueroa, Jonine D; Middlebrooks, Candace D; Banday, A Rouf et al. (2016) Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry. Hum Mol Genet 25:1203-14
Kamat, Ashish M; Willis, Daniel L; Dickstein, Rian J et al. (2016) Novel fluorescence in situ hybridization-based definition of bacille Calmette-Guérin (BCG) failure for use in enhancing recruitment into clinical trials of intravesical therapies. BJU Int 117:754-60
Sircar, Kanishka; Yoo, Suk-Young; Majewski, Tadeusz et al. (2015) Biphasic components of sarcomatoid clear cell renal cell carcinomas are molecularly similar to each other, but distinct from, non-sarcomatoid renal carcinomas. J Pathol Clin Res 1:212-24
Ke, Hung-Lung; Lin, Jie; Ye, Yuanqing et al. (2015) Genetic Variations in Glutathione Pathway Genes Predict Cancer Recurrence in Patients Treated with Transurethral Resection and Bacillus Calmette-Guerin Instillation for Non-muscle Invasive Bladder Cancer. Ann Surg Oncol 22:4104-10
(2015) Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types. J Natl Cancer Inst 107:djv279

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