Integrated genomics and comprehensive validation reveal drivers of genomic evolution in esophageal adenocarcinoma

Abstract Esophageal adenocarcinoma (EAC) is associated with a marked genomic instability, which underlies disease progression and development of resistance to treatment. In this study, we used an integrated genomics approach identify instability signature. Here show that elevated expression signature correlates poor survival in EAC as well three other cancers. Knockout overexpression screens establish the relevance these genes instability. Indepth evaluation ( TTK , TPX2 RAD54B ) confirms their role tumor growth. Mutational signatures identified by whole genome sequencing functional studies demonstrate DNA damage homologous recombination are common mechanisms induced genes. Our data suggest inhibitors possibly study have potential inhibit/reduce growth spontaneous chemotherapy-induced