Based on recently described genotype/phenotype correlations, there are likely to be several different molecular mechanisms which lead to the development of breast cancer (1). We are studying the molecular pathogenesis of early-onset breast cancer (diagnosed before 40 years), in a cohort of women enrolled in the population-based Australian Breast Cancer Family Study (ABCFS). As part of the ABCFS, the germline BRCA1 and BRCA2 mutation status of the patients has been determined. We are able to recognise clear differences in the histological appearances of BRCA1, BRCA2 and control (patients with no detectable germline mutations in the BRCA1/2 genes) cancers. In addition, the histology of the control group is less uniform than our BRCA1 and BRCA2 cancers, suggesting that their molecular pathogenesis may be more heterogeneous. Based on the above results, we are now evaluating a number of molecular parameters within this cohort, by immunohistochemical and microdissection/PCR-based molecular biological analysis in order to determine specific genetic cascades, which occur in BRCA1, BRCA2 and control cancers. We are also performing a genome-wide screen of genetic losses and gains within these tumours by the method of Comparative Genomic Hybridisation following microdissection and DOP-PCR amplification of tumour DNA. We have found that the distinct morphological appearance of BRCA1, BRCA2 and control cancers is also extended through to protein expression, with clear differences between p53 over-expression, ER and PR status in these cancers. In addition, our CGH results indicate that these three groups show different areas of genomic gain and loss. Interestingly, almost all genetic changes detected by CGH in the invasive carcinoma component of these cancers are also present in the accompanying, pre-invasive, carcinoma in situ phase of the disease.
|Number of pages||1|
|Journal||Australian Journal of Medical Science|
|Publication status||Published - 1 Dec 2000|