Abstract

Next Generation DNA Sequencing in Probing Tumour Origins and Behaviour in Haematological Malignancy

Surinder Sahota, Associate Professor/Reader, University of Southampton

Next generation sequencing (NGS) is providing an unparalleled insight into the mutated tumour genome that is heritable by malignant progeny, and which propagates disease. At the whole exome sequencing (WES) level, NGS provides specific insights into how genes are dysregulated that allow both functional studies and predictions, as well as identifying cellular and molecular pathways for new therapeutics. These data are also pivotal to understanding tumour origins and progression. My presentation will focus on haematological malignancy, and in particular on mature B-lymphoid neoplasms, and will describe NGS approaches that have allowed unique insights into origins of human multiple myeloma (MM), a disease of malignant plasma cells that accumulate in the bone marrow, and remains essentially incurable. It will review key elements of the MM genome as have emerged from NGS studies, and our work where we have profiled the tumour clone in response to therapy. These findings have profiled tumour cells at the whole population level, but it is abundantly clear that NGS of the tumour genome will now need to increasingly focus on the single cell level, to fully delineate mechanisms of tumour evolution and response to therapy. This approach which will be essential to provide individualised therapy in cancer patients.