Genetic Analysis of Human Breast Cancer
Final rept. 15 Jul 94-15 Jul 98
COLD SPRING HARBOR LAB OF QUANTITATIVE BIOLOGY NY
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The genetic abnormalities that accumulate in tumor cells are potential clues to their evolution. To identify such abnormalities, we have developed RDA representational difference analysis, a method that selects small restriction fragments present in only one of two genomic DNAs, or present in one in higher copy number. When nearly pure tumor DNA driver is used in excess to subtract normal DNA from the same individual tester, RDA yields fragments deleted in the tumor. When tester and drivers are reversed, RDA yields fragments amplified in tumor DNAs. DNA was extracted from the nuclei of about 20 breast cancer biopsies, sorted into diploid and aneuploid fractions by flow cytometry. From these pairs, we derived probes for about a half dozen loci that appear to undergo homozygous deletion. Some of the loci of deletion are also sites for high frequency loss of heterozygosity. The PTEN tumor suppressor gene was identified from one of these loci. P-TEN encodes a protein and phospholipid phosphatase.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research