Differential effects of NRasQ61 mutations on melanoma
Date
2019-05
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Publisher
The Ohio State University
Abstract
Melanoma rates have been rising for the past 30 years, with more than 96,000 new cases expected to be diagnosed in 2019. No therapeutic options are widely effective for the 15-20% of melanoma that are driven by oncogenic NRAS mutations. NRAS codon 61 mutations are commonly found in melanomas, while mutations at other codons are predominant in other cancers, such as Acute Myeloid Leukemia. A more comprehensive understanding of the differential role of NRAS mutants could advance efforts to find more effective treatments. Further exploration of differences between melanoma-common and -uncommon mutations could allow significant progress in development of therapeutic options, such as gene therapy. I hypothesized that melanoma-common mutations in humans also drive melanoma in mice. This hypothesis was tested by investigating the in vivo and in vitro variance between NRAS mutations that promote melanoma and those that do not, in order to enable the possible development of new cancer treatments. Genetically Engineered Murine Models (GEMMs) with different NRas mutations were treated and observed in order to determine which mutations drive melanomas over others. NRasQ61K and NRasQ61R mutant mice were found to drive melanoma better than mutants that were less common in the human disease. Since pathways downstream of Ras are associated with proliferation, immunofluorescence staining to detect the incorporation of EdU into proliferating cells was performed on skin sections from mice expressing various oncogenic NRas mutations. There was no significant difference in the EdU incorporation rates observed in different mutants’ skin. These findings extend our understanding of the role of NRAS in melanoma and open the door for future studies.
Description
Second place Pelatonia prize at 2019 Denman Undergraduate Research Forum
Third place in Toward Precision Cancer Medicine category at 2019 Denman Undergraduate Research Forum
Third place in Toward Precision Cancer Medicine category at 2019 Denman Undergraduate Research Forum
Keywords
melanoma, NRAS, mouse model, immunofluorescence, cancer