Research project Genotype-phenotype correlations among subclones within tumors

We aim to test the hypothesis of using multiplexed gene expression and mutation profiling by in situ sequencing (ISS) for improved diagnostics and guidance of precision therapy in breast cancer. We believe that by spatially resolving molecular profiles (genotypes) and linking these to tumor morphology and local gene expression (phenotypes), we can improve the prognostic and predictive impact of gene signatures, and thereby, the patient stratification in oncology treatment practices. Our assumption is that by identifying subclones of cancer cells and molecularly characterizing them and their respective microenvironment, we will greatly increase the probability of finding predictive and prognostic profiles for targeted therapies.

The aim is to introduce a new type of genotype-phenotype diagnostic assay that could be applied to heterogeneous tumor types where personalized diagnostics are of high clinical relevance. We will also create 3D models of genetically heterogeneous tumors with respect to their full cellular content, taking subclones of cancer cells, and their influence on their local microenvironment into account.