TRACERx

TRACERx, led by Charles Swanton at the UCL Cancer Institute and the Francis Crick Institute with Mariam Jamal-Hanjani as lead clinician, took multiple regions from each resected lung cancer and sequenced them. The first 100 tumours, across 327 regions, showed that driver mutations in EGFR, MET, BRAF and TP53 were almost always clonal, but that heterogeneous drivers arriving later in evolution were present in more than three quarters of tumours, and that elevated copy-number heterogeneity carried a hazard ratio of 4.9 for recurrence or death.

The 421-patient analysis found 22 of 40 common cancer genes under significant subclonal selection in adenocarcinoma, subclonal whole-genome doubling in 19 percent of tumours, and, strikingly, that 8 percent of lung adenocarcinomas in people with a smoking history carried no tobacco mutational signature and behaved molecularly like never-smoker tumours. The PEACE autopsy programme extended the work to death: 501 samples from 24 people covering 70 percent of the metastases visible on imaging showed that in 62.5 percent of patients several primary subclones disseminated independently, and that more than half the metastases sampled had been seeded by other metastases rather than by the primary. The same group's air pollution work then showed oncogenic EGFR variants in 18 percent of histologically normal lung tissue, and a mechanism by which particulates promote them.