Luke is a PhD student in the MB/PhD programme and the Wellcome Trust Studentship, supervised by Peter Campbell and Iñigo Martincorena.
Somatic Mutations in Non-Cancer Degenerative Disease
Comprehensive sequencing of cancers and pre-cancerous lesions have provided insight into the genomic landscape, evolution and heterogeneity of oncogenesis. In cancer the functional consequences of these mutations result in a selective advantage, through the development of cancer’s hallmarks, and subsequent tumour proliferation.
In recent years, sequencing of normal tissue has given insight into the clonality, mutational burden, mutational signatures and selection in healthy cells. In skin this has revealed a patchwork of clonal cells with diverse driver landscapes and pervasive positive selection. Exploration of the mutational landscape of other tissues is beginning to reveal variation between organs. Whilst the somatic mutation theory of carcinogenesis is widely accepted, the impact of somatic mutation accumulation on tissue function and non-cancer degenerative disease is not yet understood. One could hypothesise a role for somatic mutations across a spectrum of age-associated, life-style and auto-inflammatory diseases.
Type-2 diabetes, osteoarthritis and rheumatoid arthritis are three disease whose pathology may be influenced by somatic mutation. By microdissecting and exome-sequencing tissue from healthy donors and patients we aim to characterise the mutational burden, signatures, clonal dynamics and selection in diseased tissue and by doing so begin to understand the role of somatic mutations in non-cancer degenerative disease.