Kinome-wide decoding of network-attacking mutations rewiring cancer signaling.
Bottom Line: However, global analysis of these events is currently limited.Here, we identify six types of network-attacking mutations (NAMs), including changes in kinase and SH2 modulation, network rewiring, and the genesis and extinction of phosphorylation sites.We identified and experimentally validated several NAMs, including PKCγ M501I and PKD1 D665N, which encode specificity switches analogous to the appearance of kinases de novo within the kinome.
Affiliation: Department of Systems Biology, Technical University of Denmark, 2800 Lyngby, Denmark.Show MeSH
Related in: MedlinePlus
Mentions: Having defined the different NAMs, we next intended to assess their existence and abundance in cancer. We thus collected a set of 678,050 unique missense somatic cancer variants from COSMIC (version 67) (Forbes et al., 2011) and deployed ReKINect on this set to predict a large number of instances across the NAM classes (Figure 2).
Affiliation: Department of Systems Biology, Technical University of Denmark, 2800 Lyngby, Denmark.