Cis-regulatory variants in susceptibility to breast cancer

We are using our knowledge of cis-regulation in normal breast tissue to prioritise GWAS loci for functional characterisation. This approach will speed up the unveiling of the biological mechanisms at the basis of breast cancer aetilogy and will identify the causal variants, which will contribute to improved individual risk estimation. Maia et al 2009, Meyer&Maia 2008 We are also developing new tools to apply DAE studies in the discovery of new genetic risk factors for breast cancer.

Penetrance modifiers of BRCA2 germline mutations

We have recently identified a haplotype in the gene BRCA2 that is associated with protection towards developing breast cancer. Maia et al 2012 We are now insterested in characterising fully the regulatory architecture of BRCA2, in order to better understand the variable penetrance of germline-mutation carriers as well as the variable response to treatment with PARP inhibitors.

Cis-regulatory variants role in tumour biology

In our previous work we have identified that genes commonly mutated in breast cancers are regulated by cis-variation, thus being under an individual-specific control. Maia et al 2012 We have also conducted DAE studies in tumours, which have revealed extreme DAE profiles, with some tumours not expressing the mutated alleles at all, whilst others do not express the wild-type, albeit all carrying heterozygous mutations. We are now interested in understanding whether these discrepancies in allelic-expression of mutations have consequences in the tumour biology and therapy response.