The goal of this application is to establish a Biomarker Reference Laboratory (BRL) at the University of Alabama at Birmingham that will function within the EDRN to develop, modify and trouble-shoot potential methods of early detection prior to their entry into validation studies. Components of development will include conversion of methodologies to high-throughput methods, analysis of limitations, and development of standard-operating-procedures. As the core group of investigators has been drawn from the Program in Translational Research in Neoplasia in the Department of Pathology at UAB, all of these investigators are committed to, and have expertise in, the analysis of biomarkers. The group includes pathologists and basic researchers with expertise in neoplastic processes of the skin, head and neck, lung, colorectum, pancreas, breast, ovary and cervix, as well as technical expertise in, and resources for, surface- enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF-MS), multidimensional gel analysis protein purification, high-throughput ELISA, multiplex immunoassays, construction of tissue matrix arrays (spotted and tissue cylinders), computerized cytomorphometric analysis, immunohistochemistry (bright field fluorescent, confocal microscopy), in situ hybridization, single and multiplex real time quantitative PCR, other PCR techniques, immunomagnetic separations, tissue resources, and experimental design of validation studies. A key resource is expertise in analysis of the effects of patient characteristics (age, sex, race nutritional status, etc.) on disease progression. The expertise of the core investigators is complemented by the resources available though the UAB Comprehensive Cancer Center and the Center for Human Genetics as well as the four UAB SPORES. A network of extramural consultants and resources, both academic and commercial, also is described. The ability of the investigators to work collaboratively and as a resource is demonstrated in their publications. The ability of the UAB-BRL to act as a key resource within the EDRN is demonstrated by the fact that UAB has functioned successfully as a Biomarker Validation Laboratory in the current EDRN. In this role, UAB worked in the design and protocol development of the validation study of using microsatellite analysis of urine sediment in the early detection of transitional cell carcinoma of the bladder and as the primary validation laboratory of the Validation Study of the use of SELDI-TOF-MS to identify protein signatures in serum that predict the presence of adenocarcinoma of the prostate. A developmental project is proposed in which the effects of fixatives and antigen retrieval techniques on real time quantitative PCR will be determined; the ability to perform such analyses on fixed biopsy specimens and archival material would greatly enhance the development of markers of early detection. ? ?
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