Analysis of circulating tumour DNA for mutational characterisation and tracking disease progression in multiple myeloma

Multiple myeloma (MM) is a genetically complex malignancy presenting as a multi-focal disease that requires bone marrow (BM) biopsy and constant monitoring of conventional markers of tumour burden to determine treatment responses and guide therapeutic decisions. BM biopsy is invasive, subject to sampling bias and does not capture the spatial genomic heterogeneity of MM and thereby inadequate for mutational characterisation and prognostication. Furthermore, serum biomarkers are not sensitive enough or unreliable for minimal residual disease detection and for certain subsets of MM patients respectively. Cancer cells shed small amounts of DNA (circulating tumour DNA – ctDNA) into the blood stream and are known to harbour mutations representative of the tumour genome. These mutations can be utilised for tumour genome characterisation and non-invasive therapeutic monitoring of the disease, as an adjunct to currently available modalities. This project will evaluate if ctDNA can be utilised for tumour genome characterisation and disease detection to guide treatment decisions with an ultimate objective to incorporate ctDNA analysis as a routine diagnostic modality for MM.