Abstract

NGS of Bladder Cancer, the Genomic Landscape Driving Progression

Torben Orntoft, Professor, Aarhus University Hospital

Approximately half of patients with bladder cancers will develop an invasive life threatening disease, however, as in other cancers, we have no technology to separate the aggressive from the indolent cases. Deep sequencing was used on a series of bladder tumors to get insight into the progression associated changes in cell clone composition, mutational spectrum and mutational context. The mutational context clearly formed subgroups of cancers with highly different properties, pointing towards the mutation mechanism as an early parameter determining later outcome. Subclonal analysis identified an aggressive subclone in some patients having mutations in TP53, MLL, MLL2, ELF3, and DCC. Highly frequent mutations in epigenetic modifiers, lead to identification of several of these as strong predictors of clinical outcome. These may have immediate clinical implications as biomarkers for bladder cancer.