In situ genome-wide expression profiling of individual cell types. C. Kodira1, A. Sood1, L. Newberg1, A. Miller2, F. Ginty1, E. McDonough1, Y. Sui1, A. Bordwell1, Q. Li1, S. Kaanumalle1, K. Desai1, Z. Pang1, E. Brogi2, S. Larson2, I. Mellinghoff2 1) Diagnostics, Imaging & Biomedical Technologies, GE Global Research Center, Niskayuna, NY 12309, USA; 2) Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA.

   Understanding the tumor heterogeneity via probing of the key molecular alterations at the DNA, RNA and protein levels is crucial for tumor classification and linking their molecular status to appropriate therapy options. While Next Generation Sequencing (NGS) technology is extremely powerful for global characterization of tumour heterogeneity in terms of large-scale mutational and mRNA expression profiles, it is still limited in providing spatial/cellular context. Traditional immunohistochemistry (IHC) on the other hand is extremely valuable in providing cell level characterization and spatial context but is limited by the amount of information it can provide about altered genes/pathways. To address this challenge, we describe here a novel approach in extracting genome-wide expression profiles of individual cell types within a tumor while retaining information about their spatial arrangement in the tissue. This approach combines the hyperplex capabilities of a new immunofluorescence platform called MultiOmyxTM with microarray gene expression and Next Generation Sequencing (NGS) data and novel methods to derive cell-specific expression profiles. Profiles of individual cell types with similar molecular alterations can then be correlated to clinical information to predict specific outcomes. We present here preliminary results from a proof of concept breast cancer study to illustrate the utility of such a multi-omics approach for better understanding of tumor heterogeneity. We believe our approach is a powerful research tool for enabling biomarker discovery, therapy matching and potentially cancer management.