DID YOU KNOW? DTIC has over 3.5 million final reports on DoD funded research, development, test, and evaluation activities available to our registered users. Click
HERE to register or log in.
Accession Number:
AD1122448
Title:
Elucidating Clonal Competition Through Fluorescent Color Coding of Melanoma Cells
Descriptive Note:
[Technical Report, Final Report]
Corporate Author:
MASSACHUSETTS GENERAL HOSPITAL BOSTON
Report Date:
2020-12-01
Pagination or Media Count:
19
Abstract:
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.
Distribution Statement:
[A, Approved For Public Release]
