William D. Foulkes, MB.BS, PhD

Our research program aims to identify the genetic lesions that increase the risk for cancer development in individuals and families. We use both a personalized approach, where we perform genome-wide analyses of single individuals or families to correlate genotypes and phenotypes, as well as molecular approaches, where we study the impact of genetic lesions on cellular processes to assess the pathogenic potential of genetic variants.

The specific research areas in the laboratory include:

• DICER1 tumour predisposition syndrome (DTPS): Since 2010, our group contributed several manuscripts to the description of the types of germline and somatic mutations leading to DTPS and the associated phenotypes in affected families. Current on-going projects use model systems to elucidate the impact of selected genetic variants on miRNA and mRNA profiles as the underlying mechanism causing DTPS-related tumours.
• Rare familial and multiple primary tumours: Families / individuals with multiple rare or unusual cancer phenotypes have a high likelihood to carry a predisposing genetic lesion. We optimized the performance and analysis of whole exome sequencing of formalin-fixed, paraffin-embedded tumors to perform normal-tumour analyses of unsolved patients from the clinic and the literature.
• Leveraging mutational signatures to identify cancer predisposition alleles: Cancers that are deficient in homologous DNA repair have unstable genomes filled with unrepaired mutations. These form a footprint, or signature, which can be recognized bioinformatically from tumour sequencing data. We are using bioinformatic strategies leveraging mutational signature data to identify driver variants in novel or unrecognized genes that cause cancer predisposition.