CONSISTENT LOSS OF THE WILD-TYPE ALLELE IN BREAST CANCERS FROM A FAMILY LINKED TO THE BRCA2 GENE ON CHROMOSOME 13Q12-13

A small proportion of breast cancer is attributable to the inheritance of dominant, high penetrance susceptibility genes. One of these genes , BRCA2, has recently been localised by genetic linkage analysis to ch romosome 13q12-13, This is a region known to exhibit loss of heterozyg osity in 20-40% sporadic breast cancers, In this study, we have examin ed cancers from a family showing strong evidence of linkage to BRCA2. LOH was seen in seven out of eight informative cancers, In all cases t he allele lost was the wild type allele that does not segregate with t he disease in the family. The data suggest that both alleles of BRCA2 are inactivated in cancers, the pattern expected of a recessive oncoge ne or tumour suppressor gene.