Elucidating Clonal Competition Through Fluorescent Color Coding of Melanoma Cells
Abstract
Tumor evolution fundamentally reflects the expansion and contraction of composite clones. A driving force behind tumor sculpting is intratumoral competition, which facilitates the stratification of clones into winners and losers. The purpose of this grant is to understand clonal dynamics as a cornerstone piece of tumor evolution. Our scope is to use fluorescent-labeled cells (melachroma cells) to observe cellular competition in the context of genetic and epigenetic analysis. In Year 1, we made several important findings. First, we deployed a triple competition experiment and established the presence of a predetermined winner independent of color selection. This suggests that the potential winner population may be hard-wired either 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 the observed antagonism. These findings are currently under review in a manuscript. Finally, using melachroma cells, we determined that there is a reproducible population of cells which is inherently sensitive to MAPK inhibition. Clonal dynamics has been a cornerstone of the tumor evolution theory and our studies to date indicate an intricate interplay between cellular competition and genetic interaction.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2018
- Accession Number
- AD1060307
Entities
People
- Hensin Tsao
Organizations
- Massachusetts General Hospital