Divergent structural genomic instability trajectories in mesothelioma: linking tumour evolution to socioeconomic and occupational health inequalities
Supervisors
Prof Kevin Blyth, School of Cancer Sciences, University of Glasgow
Dr Tony Robertson, School of Health and Wellbeing, University of Glasgow
Prof Colin Semple, Institute of Genetics and Cancer, University of Edinburgh
Summary
Mesothelioma is an asbestos-driven cancer with a median survival of around one year. The UK currently has the world's highest incidence, reflecting historical asbestos utilisation and ongoing environmental exposures. Genomic instability is prominent in the mesothelioma genome but the structural variation landscape has been poorly characterized to date (including features such as large-scale rearrangements, chromothripsis, whole-genome doubling and extrachromosomal DNA). Recent work by the Semple lab (UofE supervisor) in high-grade serous ovarian cancer (HGSOC) has revealed distinct structural evolutionary trajectories that correlate with survival. This project test will determine whether similar evolutionary trajectories exist in meosthleioma using a unique, deeply phenotyped cohort of 555 patients recruited from 32 UK centres via the Meso-ORIGINS study, as part of the PREDICT-Meso International Accelerator Project (led by Blyth, UofG primary supervisor). Critically, mesothelioma is defined by marked socioeconomic gradients reflecting differing patterns of asbestos exposure, providing a unique opportunity to examine whether structural genomic variation is modified by, or correlates with health inequalities (ex-asbestos workers (typically older, male, higher deprivation) v environmental or cosmetic talc exposures (typically younger, female, more affluent). The student will join a well-resourced, interdisciplinary Glasgow–Edinburgh supervisory team, combining clinical/tissue-resource expertise, structural variation bioinformatics, and health inequalities methodology.
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