Integrative single-cell (epi)genomics and transcriptomics to understand the biology of cellular heterogeneity in melanoma over the course of treatment

Malignant melanoma is one of the most common and lethal cancers of young persons in the developed world. Melanoma tumors are comprised of a diverse set of cancer cells, and is characterized by resistance to both conventional and targeted therapy, most likely due to the heterogeneous nature of the melanoma tumor cell population. This intra-tumoral cellular heterogeneity arises through genome, epigenome and transcriptome alterations during development and progression of the tumor. Past analyses have been limited by the necessity to analyze cells in bulk, precluding detailed study of the nature, extent and biology of cellular heterogeneity in cancer. This knowledge is paramount in the design of more effective treatment. Integrative analysis of the DNA- and RNA-sequences of single cells has been established by the laboratory of Assoc Prof. T.Voet and a panel of melanoma patient derived xenograft (PDX) mouse models has been developed by the laboratory of Prof. C. Marine to understand cellular resistance mechanisms to Braf and MEK inhibitor therapy. In this ideal environment, this project will develop and apply ‘genome and transcriptome’ as well as ‘epigenome and transcriptome’ sequence analyses of the same single cells at large-scale to disclose the diversity and biology of cancer cell lineages in melanoma xenografts before, during and after therapy, paving a path to more effective medecine.