Oesophageal adenocarcinoma exome sequence data from samples before and after neo-adjuvant chemotherapy

How chemotherapy affects carcinoma genomes is largely unknown. Here, we performed whole-exome and deep sequencing of 30 paired oesophageal adenocarcinomas sampled before and after neo-adjuvant chemotherapy. Most, but not all, good responders passed through genetic bottlenecks. Some poor responders also passed through bottlenecks, but re-grew by the time of surgical resection, suggesting a missed therapeutic opportunity. Several cancers showed major changes in driver mutation presence or frequency after treatment, owing to outgrowth or persistence of sub-clones, copy number changes, polyclonality and spatial genetic heterogeneity. The post-treatment samples of good responders or bottleneckers showed a mutation spectrum shift to C>A and TT>CT, and several of these harboured mutations in known cancer driver genes (for example, SF3B1, TAF1 and CCND2) that were absent from the pre-treatment sample. Neo-adjuvant chemotherapy can profoundly affect the EAC genome after two treatment cycles and monitoring molecular changes during treatment may be clinically useful.