Somatic mutation, clonal dynamics and tumour evolution in premalignant lung disease

Lung cancer is the leading cause of cancer-related deaths worldwide, developing in more than a million new patients each year. In the UK, more than one in five cancer deaths is due to lung cancer, with 80% of these cancers directly attributable to exposure to tobacco. Lung cancer does not form spontaneously but gradually develops over decades of exposure to the DNA-damaging chemicals in tobacco smoke.

We will use DNA sequencing technology to analyse the patterns and frequency of mutations accumulating in normal lung cells across a variety of smoking behaviours, including current smokers, reformed smokers, passive smokers and people who have never smoked. We will analyse the genome of the earliest detectable stages of pre-cancerous lung disease to identify the key initiating mutations that can drive cancer development and compare the genomes of pre-cancerous regions of the lung that ultimately progress to full cancer with regions that subsequently disappear spontaneously.

This data will help us understand the inter-relationships across tobacco exposure, accumulation of mutations and cancer evolution.