Many cancers are associated with recurrent abnormalities of chromosome structure. One abnormality, a chromosomal translocation, occurs when portions of two normal chromosomes are exchanged. In the cancer setting, translocations may change the expression of genes near the chromosomal breakpoint, or may cause an abnormal """"""""fusion oncogene"""""""" to be formed when portions of two genes at the breakpoint become linked together in an abnormal way. The products of these fusion oncogenes induce cancer development in the cells where they occur. In many instances, the presence of these fusion oncogenes may provide diagnostic, prognostic, or therapeutic information about the tumor. A highly sensitive and specific approach for detecting these chromosomal translocations would allow new information to be developed about cancers that contain them, and would also be of great use to the clinical care of these patients with these tumors. Unfortunately, although current approaches have been useful in detecting translocations and their products, they have a number of shortcomings that limit their use. We now propose to develop a new approach for translocation detection that avoids many of the difficulties associated with current methods: antibody detection of translocations (ADOT). We plan to develop two versions of this technology, one that can analyze thousands of potential translocations at a time, but is somewhat costly, and one that can analyze a limited number of translocations at once, but is relatively cheap. We will determine the functional characteristics of these approaches, and compare them to current methodologies. At the end of these studies, we will have developed and characterized a technique for detecting these important chromosomal abnormalities that may be ready for clinical and research applications.
Chromosomal translocations are a type of genetic mutation that are highly associated with the development of human cancers. Detection of translocations, then, has important implications for the diagnosis of cancer, for providing prognostic information to patients with this disease, and in some cases, for deciding on the appropriate anti-cancer treatment for patients. We propose to develop a new technology that will circumvent many of the shortcomings associated with current technologies for translocation detections, and thus provide critical information to improve the care of patients with cancer.
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