Anthony Uren
Imperial College, UK
Determining recurrent and rare cancer mutations which are bona fide driver mutations remains a bottleneck in cancer research. Here, we present the most comprehensive analysis of retrovirus driven lymphomagenesis produced to date, sequencing 700,000 mutations from more than 500 malignancies collected at time points throughout tumor development. This enabled identification of positively selected events, and the first demonstration of negative selection of mutations that may be deleterious to tumor development (e.g. Smyd3) indicating novel avenues for therapy. Customized sequencing and bioinformatics methodologies were developed to quantify sub-clonal mutations in both premalignant and malignant tissue, greatly expanding the statistical power for identifying driver mutations and yielding a high-resolution, genome wide map of the selective forces surrounding cancer gene loci. Screening two BCL2 transgenic models confirms known drivers of human B-cell non-Hodgkin lymphoma, and implicates novel candidates including modifiers of immuno-surveillance such as co-stimulatory molecules (Cd86, Icosl and PD-1) and MHC loci. Correlating mutations with genotypic and phenotypic features also gives robust identification of known cancer genes independently of local variance in mutation density.
Anthony Uren has completed his PhD from the Walter and Eliza Hall Institute, followed by Post-doctoral positions at Genentech and at the Netherlands Cancer Institute. He is currently a Principal Investigator at the MRC London Institute of Medical Sciences at Imperial College.
Email: anthony.uren@imperial.ac.uk
