Cancer as Competing Clones: Theoretical and Experimental Cellular Sociology
>Systems Biology Free

B30

The pre-invasive neoplastic development process is one of competing normal and molecularly evolving clonal populations. These altered competing cells are recapitulating their internal molecular dynamics and interactions at the physical level through increased growth, decreased apoptosis, resource request signaling and usage, as well as interacting with the host immune system and surrounding stroma. An in depth understanding of all these interactions is key to understanding and altering the neoplastic process for therapeutic (chemoprevention for pre-neoplastic tissue and chemotherapy for invasive cancer) purposes.
 >We are developing a two prong approach to this problem; 1) a computational 3D static and dynamic model of tissue epithelium and stroma (based on physical and molecular interactions) and 2) an automated system for multi-colour FISH of tissue sections for the identification of genetically related clones in excised tissue samples.
 >Our current mathematical model is based on quantitative data from the nuclear phenotypes of the cells, molecular characteristics from quantitative IHC and quantitative tissue architectural information (spatial arrangement of cells in tissue) from more than 10,000 of lung, cervix and oral sections.
 >The automated system for multi-colour FISH is designed to scan up to 6 FISH labels automatically across an entire tissue section and analyze the results cell by cell and then by clonal neighbourhood. Several versions of clonal neigbourhood have been tested. These are derived from the Voronoi tessellation of the imaged tissue based upon the spatial arrangement of the individual cells and their FISH attributes. Initial testing of this system showed clonal populations of cells resistant to lung cancer chemotherapy based upon a specific gene copy number alteration profile, derived form array CGH data.