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Activation of K-RAS by co-mutation of codons 19 and 20 is transforming.

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Naguib, Adam 
Wilson, Catherine H 
Adams, David J 
Arends, Mark J 


The K-RAS oncogene is widely mutated in human cancers. Activating mutations in K-RAS give rise to constitutive signalling through the MAPK/ERK and PI3K/AKT pathways promoting increased cell division, reduced apoptosis and transformation. The majority of activating mutations in K-RAS are located in codons 12 and 13. In a human colorectal cancer we identified a novel K-RAS co-mutation that altered codons 19 and 20 resulting in transitions at both codons (L19F/T20A) in the same allele. Using focus forming transformation assays in vitro , we showed that co-mutation of L19F/T20A in K-RAS demonstrated intermediate transforming ability that was greater than that of individual L19F and T20A mutants, but less than that of G12D and G12V K-RAS mutants. This demonstrated the synergistic effects of co-mutation of codons 19 and 20 and illustrated that co-mutation of these codons is functionally significant.



0601 Biochemistry and Cell Biology, Biomedical, Basic Science, Colo-Rectal Cancer, Cancer, Genetics, Digestive Diseases, Cancer, 2.1 Biological and endogenous factors

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J Mol Signal

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Journal of Molecular Signaling