Background:

Family history is a well established risk factor for prostate cancer.  BRCA2 mutation carriers have been shown to present with more aggressive prostate cancer and have a poor survival.  Recent advances in laboratory and bio-informatics enable us to investigate and understand the pathways involved in tumour genesis and potentially identify new clinical markers for treatment.

Results:

Our group has recently performed whole genome Copy Number Analysis (CNA) on tumour and normal tissue from BRCA2 carriers and identified a number of areas of genetic instability.  Some of the areas of instability identified are within the regions of the genome where known tumour suppressor genes are located such as chromosome 8, 10 and 13. Using the same tumour tissue DNA for further somatic mutation analysis, we now plan to utilize a custom built targeted gene panel that contains numerous common “hot spot” tumour suppressor genes. .  Many of the genes represented on the targeted Illumina gene panel are linked to new “actionable” mutations which are defined as mutations that may be amenable to (gene) targeted therapies.

 Conclusion:

We aim to analyse tumour tissue DNA from BRCA2 carriers for mutations in these known genes to a) further characterise the whole genome instability that occurs in these prostate cancers to potentially map the pathways involved in the tumour genesis in pathogenic BRCA2 mutation carriers and b) to see if these men have “actionable” mutations that may be suitable for a targeted therapy.