Use of monozygotic twins in search for breast cancer susceptibility loci.
We have used Swedish monozygotic twins concordant for breast cancer to study genetic changes associated with the development of breast cancer. Because loss of heterozygosity (LOH) at a specific genomic region may reflect the presence of a tumour suppressor gene, loss of the same allele in both of the twins concordant for breast cancer may pinpoint a tumour suppressor gene that confers a strong predisposition to breast cancer. DNA samples extracted from the matched tumour and normal tissues of nine twin pairs were analysed for allelic imbalance using a set of microsatellite markers on chromosomes 1, 13, 16 and 17, containing loci with known tumour suppressor genes. The two main regions, where more twin pairs than expected had lost the same allele, were located at 16qtel', including markers D16S393, D16S305 and D16S413, and at 17p13, distal to the p53 locus. Our results show that the monozygotic twin model can be used to suggest candidate regions of potential tumour suppressor genes, even with a limited number of twin pairs.
Försti
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A
Department of Biosciences at Novum, Karolinska Institute, SE-14157 Huddinge, Sweden. asta.forsti@cnt.ki.se
Jin
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Sundqvist
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L
Söderberg
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M
Hemminki
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K
D000328:Adult; D000368:Aged; D000483:Alleles; D024682:BRCA2 Protein / Q000302:isolation & purification; D016010:Binomial Distribution; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1; D002882:Chromosomes, Human, Pair 13; D002886:Chromosomes, Human, Pair 17; D016001:Confidence Intervals; D004200:Diseases in Twins / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1 / Q000502:physiology; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008875:Middle Aged; D012042:Registries; D013548:Sweden / Q000453:epidemiology; D014430:Twins, Monozygotic / Q000235:genetics*
D024682:BRCA2 Protein; D005819:Genetic Markers