Quantitation of Allelic Imbalance in Solid Tumors

Allelic loss or "loss of heterozygosity" (LOH), a type of genetic abnormality in tumor cells, is amarker of tumor suppressor mutation and 1 or genomic instability in the genesis or progression of humancancers. Allelic losses of certain genetic regions, and an index of whole-genome allelic loss, have beenshown to be good predictors of distant metastasis and survival in colorectal cancer, but clinicalapplication is hindered by several technical drawbacks of traditional LOH methods. The overall objectiveof this study is to improve methods for measuring allelic loss and to demonstrate practical uses for suchmeasurement. With the use of PcR-based microsatellite repeat polymorphism and quantitative phosphorimaging 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-upof such procedures to allow rapid measurement of genome-wide allelic loss. These studies could leadto new applications in cancer research and clinical medicine.