A Comprehensive Survey of Ras Mutations in Cancer
Top Cited Papers
- 14 May 2012
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 72 (10), 2457-2467
- https://doi.org/10.1158/0008-5472.can-11-2612
Abstract
All mammalian cells express 3 closely related Ras proteins, termed H-Ras, K-Ras, and N-Ras, that promote oncogenesis when they are mutationally activated at codon 12, 13, or 61. Although there is a high degree of similarity among the isoforms, K-Ras mutations are far more frequently observed in cancer, and each isoform displays preferential coupling to particular cancer types. We examined the mutational spectra of Ras isoforms curated from large-scale tumor profiling and found that each isoform exhibits surprisingly distinctive codon mutation and amino-acid substitution biases. These findings were unexpected given that these mutations occur in regions that share 100% amino-acid sequence identity among the 3 isoforms. Of importance, many of these mutational biases were not due to differences in exposure to mutagens, because the patterns were still evident when compared within specific cancer types. We discuss potential genetic and epigenetic mechanisms, as well as isoform-specific differences in protein structure and signaling, that may promote these distinct mutation patterns and differential coupling to specific cancers. Cancer Res; 72(10); 2457–67. ©2012 AACR.Keywords
This publication has 66 references indexed in Scilit:
- Allosteric Modulation of Ras-GTP Is Linked to Signal Transduction through RAF KinaseOnline Journal of Public Health Informatics, 2011
- Association of KRAS p.G13D Mutation With Outcome in Patients With Chemotherapy-Refractory Metastatic Colorectal Cancer Treated With CetuximabJAMA, 2010
- COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in CancerNucleic Acids Research, 2010
- Allosteric modulation of Ras positions Q61 for a direct role in catalysisProceedings of the National Academy of Sciences of the United States of America, 2010
- Integration of multiple signaling pathway activities resolves K-RAS/N-RAS mutation paradox in colon epithelial cell response to inflammatory cytokine stimulationIntegrative Biology, 2010
- The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulationCurrent Opinion in Genetics & Development, 2009
- Ras acylation, compartmentalization and signaling nanoclusters (Review)Molecular Membrane Biology, 2009
- Mapping the Nucleotide and Isoform-Dependent Structural and Dynamical Features of Ras ProteinsStructure, 2008
- Transformation Efficiency of RasQ61 Mutants Linked to Structural Features of the Switch Regions in the Presence of RafStructure, 2007
- Ras proteins: paradigms for compartmentalised and isoform-specific signallingCellular and Molecular Life Sciences, 2007