QUANTITATION OF ALLELIC IMBALANCE IN SOLID TUMORS

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Allelic loss or "loss of heterozygosity" (LOH), a type of genetic abnormality in tumor cells, is a marker of tumor suppressor mutation and 1 or genomic instability in the genesis or progression of human cancers. Allelic losses of certain genetic regions, and an index of whole-genome allelic loss, have been shown to be good predictors of distant metastasis and survival in colorectal cancer, but clinical application is hindered by several technical drawbacks of traditional LOH methods. The overall objective of this study is to improve methods for measuring allelic loss and to demonstrate practical uses for such measurement. With the use of PcR-based microsatellite repeat polymorphisms and quantitative phosphor imaging analysis, we will investigate the feasibility of detecting allelic imbalances in archival (formalin-fixed, paraffin-embedded) clinical prostate cancer specimens, and of automation and scale-up of such procedures to allow rapid measurement of genome-wide allelic loss. These studies could lead to new applications in cancer research and clinical medicine.