2017 Fiscal Year Annual Research Report
Hotspot Synonymous Cancer Mutations Part 1: Effect on Cap-independent Translation of New HRAS Isoform
| Project/Area Number |
16K21111
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Keywords | cancer / HRas / HRas mRNA / HRas isoform / IRES / synonymous mutation / p14HRas / bladder cancer |
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| Outline of Annual Research Achievements |
Ras genes are the most mutated proto-oncogenes in cancer. Here we identified a new Ras protein: p14HRas. We identified the mechanisms of regulation of p14 and investigated p14’s upregulation in cancer. We discovered the mechanism of action of a previously uncharacterized cancer-specific mutation in Ras; the 4th most common mutation in HRas. We estimated the incidence of this mutation in bladder cancer and found an association between the mutation, p14 expression and cancer grade and genomic instability. We propose a new mechanism for oncogenicity in cancer involving a new proto-oncogene (p14HRas), a new mutation (present in 50% of bladder cancers) and an alternative translation mechanism. Further studies can be aimed at targeting p14HRas for therapy in half of bladder cancer patients.
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