gms | German Medical Science

Objectives: The tumour suppressor genes BRCA1 and BRCA2 are responsible for almost 50% of hereditary breast carcinomas. In families with proven mutations in one of the susceptibility genes accumulate not only breast and ovarian carcinomas but also other tumour entities. To analyse a causal relationship between the associated tumours and the familial BRCA mutation, we investigated tumour tissue of family members: primarily to prove the mutation status (Cosegregation) and secondly to verify a loss of the wild type allele (LOH).

Patients/Methods: We investigated paraffin embedded material from 135 carcinomas (CA) of 118 patients from families with proven mutations in BRCA1 (n=98) and BRCA2 (n=37), including 91 breast CA, 13 ovarian CA, 6 skin CA, 7 colon CA, 6 pancreas CA, 4 prostate CA, 2 kidney CA, 2 cervical CA, one mullerian adenosarcoma, one CA of the fallopian tube, one parotis CA and one non-Hodgkin lymphoma. The DNA extraction was followed by PCR and the PCR products were directly sequenced forward and reverse on a semiautomated sequencer. The primers were designed to flank fragments with a maximum length of 250 bp.

Results: We initially investigated 18 tumours in eight families. In 10 breast CA, 3 ovarian CA, 2 colon CA, one pancreas CA and the mullerian adenosarcoma we could reveal the loss of the wild type allele and the retention of the mutated allele. In three cases (2 colon CA and one pancreas CA) we could detect both the LOH and the mutation (Cosegregation).

Conclusion: Our hitherto results corroborate the hypothesis of a causal relationship between the associated tumours and the BRCA mutation and that mutations in the BRCA1 and BRCA2 gene count for a higher risk for different tumour entities. These results could lead to a sophisticated counselling and surveillance programme for affected families.