Broad study of 2,658 patients, involving 39 types of cancer, has described mutations landscape.
Cancer diseases on every stage are inevitably associated with genome mutations. As every cell division introduces a few new mutations, the risk of cancer disease dramatically increases during lifetime. Most of cancer cases begin to emerge after 50. year of life.
Evolutionary history of 2,778 cancers from 2,658 individuals revealed details of mutation aggregation in time. Changes of DNA sequences were divided to:
- Early clonal mutations – emerged before gene copies alterations and before separation of tumor cells population,
- Late clonal mutations – introduced after gene copies changes and still before tumor emergence,
- Subclonal mutations – observed in only fraction of cancer cells.
On a basis of sequence changes in cancer cell populations, there was possible to assess time of mutation emergence.
For all cancers, most common early mutations concern gene TP53 and chromosome 17.
Timing of the earliest mutations is very variable between individuals: from a few years before diagnosis to even two decades. Most of patients had initial mutations nearly ten years before diagnosis. After disease detection, which typically occurs in later stages of cancer, mutations aggregate in pace of around 5 times faster than in previous period.
Overall, the study points to a possibility of extremely early cancer detection by genome mutation analysis.
More: “The evolutionary history of 2,658 cancers”, M. Gerstung et al., 2018, doi:10.1101/161562.