USE OF TWINS IN SEARCH FOR TUMOR-SUPPRESSOR GENES

A new approach is applied in the mapping of tumor suppressor genes: an alysis of toss of heterozygosity (LOH) in concordant tumors of monozyg otic and dizygotic twins. The method relies on recognition of genome l ocations undergoing loss in both twins in a high proportion of the set of all twin pairs examined. The method effectively pinpoints, and exc ludes, the loci of potential tumor suppressor genes. With the help of a high density linkage map any such candidates can be placed within a narrow region of a chromosome arm and perhaps matched with known genes . The analysis of the Swedish Twin Registry has shown a clear genetic component for breast cancer. We have identified mono-and dizygotic twi ns concordant for breast cancer and collected the pathology specimens. Tumor and normal tissue was microdissected and microsatellite analysi s carried out to test for allelic loss (LOH) in entirely new and putat ive chromosomal loci in this cancer. It can be calculated that using o nly six pairs of informative monozygotic twins, a locus can be incrimi nated with a high probability. Using increasingly dense markers and se arch for homozygous deletions, it should be possible to map one or mor e candidates for breast cancer. (C) 1997 Wiley-Liss, Inc.