GENOME SCANNING OF BREAST CANCERS BY 2-DIMENSIONAL DNA TYPING

We have recently used two-dimensional DNA typing to detect genetic alt erations in breast tumours. This method, which is based on size separa tion in neutral gels and sequence separation in denaturing gradient ge ls followed by hybridisation analysis with mini- and microsatellite co re probes, allows the simultaneous analysis of hundreds of allelic fra gments in a very short time. Here we demonstrate the potency of this m ethod for,total genome scanning of the tumour genome by analysing a sm all series of breast cancers. Comparison of tumour and normal DNA from ten breast cancer patients, using two-dimensional DNA typing with fou r core probes, revealed a considerable number of genomic alterations. In contrast, with Southern blot analysis only a few alterations were o bserved using the same probes. Most of the changes observed (74%) were deletions (absence of spots in the tumour) while 20% corresponded to amplifications (spots of higher intensity in the tumour) and 5% were n ew spots (gains). About 10% of the genomic changes detected appeared t o occur in the tumours of more than one patient.