Abstract
Loss of heterozygosity (LOH) on chromosome 13 occurs on 25-30% of breast tumours. This may reflect the inactivation of the retinoblastoma susceptibility gene RB1. However, recently another candidate tumour-suppressor gene has been identified on chromosome 13 by linkage analysis, the breast cancer susceptibility gene BRCA2. To investigate the involvement of BRCA2 in sporadic breast cancer 200 breast tumours were tested for LOH on chromosome band 13q12-q14, using 11 highly polymorphic microsatellite markers. LOH was found in 65 tumours, which all showed simultaneously loss of BRCA2 and RB1. Of 12 breast tumour cell lines tested with polymorphic microsatellite markers, seven showed a contiguous region of homozygosity on 13q12-q14, suggesting LOH in the tumour from which the cell line had been derived. One cell line showed homozygosity in the BRCA2 region and heterozygosity at RB1. This is the only indication that BRCA2 is a distinct target for LOH on chromosome 13 in addition to RB1.
Highlights
S _qary Loss of heterozygosity (LOH) on chromosome 13 occurs on 25-30% of breast tumours
To mvestigate the mvolvement of BRCA2 in sporadic breast cancer 200 breast tumours were tested for LOH on chromosome band 13ql2-ql4, ing 11 highly polymorphic microsatellite markers
Loss of heterozygosity (LOH) on chromosome 13 occurs in approximately 25% of primary breast tumours (Devilee and Cornelisse, 1994)
Summary
The 13ql2-ql polymorphic microsatellite markers used were D13S289, D13S290, AFM238zd, AFM109xhl, D13S260, D13S171, D13S267, D13S219, D13S218, D13S155 and D13S153 (within RB)). (Gyapay et al, 1994; J Weissenbach, personal communication). Molecular Dynamics Im uaNT Software was used for quantification of PCR products. The allelic imblanc (Al) factor is the quotient of the peak ratio from tumour and constitutional DNA. The tumour cell lines had no corresponding normal DNA with which to compare the results. The publshed allele frequencies of each alele at all markers were used to calculate the probability of the wild-type DNA being homozygous at each locus. It was possible to calculate the probability of the DNA being homozygous throughout the BRCA2 and RBI regions in the germine DNA (Table I), e.g. the probability that cell line MDA157 has a contiguous zone of homozygosity for the markers D13S260, S171, S267, S219 and S218 is
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