| description |
It is frequently assumed that pre-invasive lesions are simpler precursors of cancer, and will contain a limited subset of the genomic changes seen in their associated invasive disease. Driver mutations are thought to occur early, but it is not known how many of these are present in pre-invasive lesions. These assumptions need to be tested with the increasing focus on both personalised cancer treatments, and early detection methodologies.We examined genomic copy number changes in 256 pre-invasive and invasive samples from 69 oral cancer patients. Forty-eight samples from 16 patients were further examined using exome sequencing. From the copy number data, 95% of patients showed evidence of a shared ancestor of the dysplasia and carcinoma samples. A third of dysplasia samples showed evidence of a shared ancestor with the associated carcinoma, but with subsequent divergence. Of the remainder, most low-grade dysplasia genomes did appear to be a simpler precursor to the carcinoma, whilst most high-grade dysplasias were identical to their associated carcinoma.From the exome data, the carcinoma samples all had more somatic mutations that their associated dysplasias. The number of total, and shared mutations varied hugely between patients, even for putative driver mutations. The one exception was TP53, which, where present, was nearly always an early event, shared between samples.These results show that carcinoma and associated dysplasia samples have a common clonal ancestor, but that there is considerable diversity in the relationships between associated pre-invasive and invasive disease. For some patients, dysplasia is a simple precursor of cancer. For others, even low-grade dysplasia genomes have most of the changes seen in the invasive carcinoma. There is also frequent considerable divergence of dysplasia genomes since the most recent shared ancestor with the carcinoma. |