Detection of genomic alterations in human endometrial cancer by two-dimensional gel electrophoresis.

OBJECTIVE: The purpose of this study was to detect genomic alterations in human endometrial cancer by two-dimensional gel electrophoresis. STUDY DESIGN: With use of a newly developed two-dimensional gel electrophoresis assay, we scanned 19 high-risk DNA fragments for alterations in human endometrial hyperplasias and adenocarcinomas. This method includes cleaving of high-molecular-weight DNA, radioactive labeling, and separating DNA fragments by two-dimensional gel electrophoresis. By comparing the two-dimensional gel electrophoresis profile (spots) of neoplastic with normal endometrium, genetic alterations such as amplification, allelic loss, and hypermethylation or hypomethylation can be detected. RESULTS: Seven of 8 human endometrial adenocarcinoma (88%) and 1 of 2 hyperplasias (50%) revealed changes in spot density. The number of spots changed per specimen was 4. The median percentage of specimens with changes in an individual spot was 30%. Eleven spots had a reduction or loss of spot density, and 8 spots had an increase in spot density. CONCLUSION: By use of a novel two-dimensional gel electrophoresis assay, we identified genetic alterations in 50% of hyperplasias and 88% of endometrial adenocarcinomas.