Genomic and transcriptomic alterations associated with drug vulnerabilities and prognosis in adenocarcinoma at the gastroesophageal junction

Adenocarcinoma at the gastroesophageal junction (ACGEJ) has dismal clinical outcomes and there are currently few specific effective therapies because of limited knowledge on its genomic and transcriptomic alterations. The present study investigates genomic and transcriptomic changes in ACGEJ from Chinese patients and analyzes their drug vulnerabilities and associations with the survival time. Here we show that the major genomic changes of Chinese ACGEJ patients are chromosome instability promoted tumorigenic focal copy-number variations and COSMIC Signature 17-featured single nucleotide variations. We provide a comprehensive profile of genetic changes that are potentially vulnerable to existing therapeutic agents and identify Signature 17-correlated IFN-α response pathway as a prognostic marker that might have practical value for clinical prognosis of ACGEJ. These findings further our understanding on the molecular biology of ACGEJ and may help develop more effective therapeutic strategies. We performed bulk RNA-seq on 123 pairs of tumor and adjacent normal tissue samples obtained from 123 individuals on Illumina HiSeq X Ten platform. **Submitter declares that the raw data have been deposited in the Genome Sequence Archive (GSA) in BIG Data Center, Beijing Institute of Genomics (BIG), Chinese Academy of Sciences (https://bigd.big.ac.cn/gsa-human) under accession number HRA000025.**