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Elucidating Clonal Competition Through Fluorescent Color Coding of Melanoma Cells


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Tumor evolution fundamentally reflects the expansion and contraction of composite clones. A driving force behind tumorsculpting is intratumoral competition, which facilitates the stratification of clones into winners and losers. The purpose ofthis grant is to understand clonal dynamics as a cornerstone piece of tumor evolution. Our scope is to use fluorescent-labeledcells (melachroma cells) to observe cellular competition in the context of genetic and epigenetic analysis. In Year 1, wemade several important findings. First, we deployed a triple competition experiment and established the presence of a predeterminedwinner independent of color selection. This suggests that the potential winner population may be hard-wiredeither at a genetic or epigenetic level. Second, we proposed and confirmed that dual oncogene antagonism (i.e.BRAF* NRAS*) as a potential genetic mechanism for cellular competition; we identified SPRY4 as one mediating pathway theobserved antagonism. These findings are currently under review in a manuscript. Finally, using melachroma cells, wedetermined that there is a reproducible population of cells which is inherently sensitive to MAPK inhibition. Clonal dynamicshas been a cornerstone of the tumor evolution theory and our studies to date indicate an intricate interplay between cellularcompetition and genetic interaction.



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