Use of twins in search for tumor suppressor genes.
A new approach is applied in the mapping of tumor suppressor genes: analysis of loss of heterozygosity (LOH) in concordant tumors of monozygotic and dizygotic twins. The method relies on recognition of genome locations undergoing loss in both twins in a high proportion of the set of all twin pairs examined. The method effectively pinpoints, and excludes, 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 twins concordant for breast cancer and collected the pathology specimens. Tumor and normal tissue was microdissected and microsatellite analysis carried out to test for allelic loss (LOH) in entirely new and putative chromosomal loci in this cancer. It can be calculated that using only six pairs of informative monozygotic twins, a locus can be incriminated with a high probability. Using increasingly dense markers and search for homozygous deletions, it should be possible to map one or more candidates for breast cancer.
Försti
A
A
Department of Biosciences, Karolinska Institute, Novum, Huddinge, Sweden.
Söderberg
M
M
Hemminki
K
K
D019313:BRCA1 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D004200:Diseases in Twins; D005260:Female; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006579:Heterozygote; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D013548:Sweden; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic
D019313:BRCA1 Protein