IDENTIFICATION BY REPRESENTATIONAL DIFFERENCE ANALYSIS OF A HOMOZYGOUS DELETION IN PANCREATIC-CARCINOMA THAT LIES WITHIN THE BRCA2 REGION

Homozygous deletions have been central to the discovery of several tum or-suppressor genes, but their finding has often been either serendipi tous or the result of a directed search. A recently described techniqu e [Lisitsyn, N., Lisitsyn, N. and Wigler, M. (1993) Science 259, 946-9 51] held out the potential to efficiently discover such events in an u nbiased manner. Here we present the application of the representationa l difference analysis (RDA) to the study of cancer. We cloned two DNA fragments that identified a homozygous deletion in a human pancreatic adenocarcinoma, mapping to a 1-centimorgan region at chromosome 13q123 flanked by the markers D13S171 and D138260. Interestingly, this lies within the 6-centimorgan region recently identified as the BRCA2 locus of heritable breast cancer susceptibility. This suggests that the sam e gene may be involved in multiple tumor types and that its function i s that of a tumor suppressor rather than that of a dominant oncogene.