PO-337 Single cell mRNA sequencing reveals the presence of the gene expression signature of all major molecular subtypes in individual breast cancers

IntroductionBreast cancer is a heterogeneous disease; different tumours can have distinct pathological features and therapeutic sensitivities. Much effort has been invested to identify molecular breast cancer subtypes, with the hope to better guide treatment decisions and to improve treatment outcomes but so far with limited added value to current histopathological diagnostics. However, techniques currently used in molecular diagnostics are based on bulk measurements that obscure intra-tumoral heterogeneity, and will be dominated by the most prevalent tumour cell clone and stromal components. Therefore, it is unknown whether therapy failure is caused by positive selection of either tumour cells that acquire treatment resistance or non-responding tumour cells already present in the tumour prior to treatment.Material and methodsTo better understand this, we examine the molecular characteristics of more than 5000 individual tumours cells from ten breast cancer patients with distinct molecular subtypes of breast cancer using single cell mRNA sequencing.Results and discussionsWe found that every examined tumour contain cells expressing a gene-signature from all major breast cancer molecular subtypes, namely luminal A luminal B, Her2 +and basal, suggesting that single breast tumours contain cancer cells with differences in therapy sensitivity and response. By contrast, the expression profiles of tumor-supporting non-cancer cells in the micro-environment appeared to be remarkably similar within and between tumours and may therefore potentially serve as a therapeutic target for all breast cancer subtypes.ConclusionOur data suggest that more detailed analysis of individual cells by single cell m RNA sequencing may further improve classification and patient selection. Furthermore, we illustrate that tumor-supporting non-cancer cells in the microenvironment may serve as a potential target to eliminate co-existing populations of tumour cells that show expression profiles of distinct molecular characteristics.