Genomic variation, through its effect on gene structure and expression, plays an important role in disease predisposition, biology and clinical response to therapy. In my presentation, I will provide examples of on-going projects that emerged from large-scale genome studies of cancer that are pertinent to understanding the role of both classes of cancer mutations (inherited and acquired) in the context of early phases of cancer development and potential approaches to use this knowledge in tailored screening interventions.
I will provide examples of: 1) Models to determine colorectal cancer risk using common genetic risk markers and optimise screening strategies; 2) Deep-sequencing of acute myeloid leukemia samples used to trace the initiating mutations to infer leukemia and possible applications that will enable diagnosis of pre-leukemic states, i.e. prior to overt leukemia; 3) Cancer mutation profiles that can better distinguish aggressive and indolent forms of prostate cancer at the time of first diagnosis to reduce the overtreatment of the disease in patients with more benign forms.
In each example, I will also pose biological questions that arose in these studies, and avenues for further work to obtain a greater understanding of early cancers and transform this knowledge into tailored interventions based on the profile of the tumour and the patient.