Significance of duon mutations in cancer genomes.
Functional mutations in coding regions not only affect the structure and function of the protein products, but may also modulate their expression in some cases. This class of mutations, recently dubbed "duon mutations" due to their dual roles, can potentially have major impacts on downstream pathways. However their significance in diseases such as cancer remain unclear. In a survey covering 4606 samples from 19 cancer types, and integrating allelic expression, overall mRNA expression, regulatory motif perturbation, and chromatin signatures in one composite index called REDACT score, we identified potential duon mutations. Several such mutations are detected in known cancer genes in multiple cancer types. For instance a potential duon mutation in TP53 is associated with increased expression of the mutant allelic gene copy, thereby possibly amplifying the functional effects on the downstream pathways. Another potential duon mutation in SF3B1 is associated with abnormal splicing and changes in angiogenesis and matrix degradation related pathways. Our findings emphasize the need to interrogate the mutations in coding regions beyond their obvious effects on protein structures.
Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.|The Jackson Laboratory, Farmington, CT06032, USA.
Vinod Kumar
VK
Yadav
Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.|Computational Biosciences Graduate Program, University of Colorado, Aurora, CO 80045, USA.
Kyle S
KS
Smith
Center for Applied Molecular Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
Colin
C
Flinders
Center for Applied Molecular Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
Shannon M
SM
Mumenthaler
Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.|University of Colorado Cancer Center, Aurora 80045, CO, USA.|Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA.
Subhajyoti
S
De
D015972:Gene Expression Regulation, Neoplastic; D016678:Genome; D006801:Humans; D020125:Mutation, Missense; D009369:Neoplasms / Q000235:genetics*