Genomic evidence supports a clonal diaspora model for metastases of esophageal adenocarcinoma

The poor outcomes in esophageal adenocarcinoma (EAC) prompted us to interrogate the pattern and timing of metastatic spread. Whole genome sequencing and phylogenetic analysis of 388 samples across 18 EAC cases demonstrated in 90% of cases that multiple subclones from the primary tumor spread very rapidly from the primary site to form multiple metastases, including lymph nodes and distant tissues, a mode of dissemination that we term ‘clonal diaspora’. Metastatic subclones at autopsy were present in tissue and blood samples from earlier time-points. These findings have implications for our understanding and clinical evaluation of EAC.