The TCGA PanCanAtlas Project studied pathogenic germline variants across 10,000 cancer patients in a large international collaboration led by Kuan-lin Huang and Li Ding.
Our contribution to the project led to the discovery of novel candidate mechanisms acting on several known cancer genes and their cancer-causing inherited genetic variants. The pathogenic variants appear to alter post-translational modification (PTM) sites and kinase binding motifs in proteins. We found that PTM sites are generally mutated much more often than expected by chance alone, suggesting that alteration of PTMs and signalling networks is a widespread mechanism in inherited cancer genetics. Thus more of such variants are likely yet to be discovered. This analysis enables detailed future experiments to understand the role of these mutations altering the activity of cancer genes.
This analysis was performed using our recently published database ActiveDriverDB.org and was led by Marta Paczkowska and Michal Krassowski.
The publication is available at https://www.cell.com/cell/abstract/S0092-8674(18)30363-5 (see Figure 6 and related materials)