Extrachromosomal DNA amplifications exhibit distinct molecular characteristics and prognostic implications in gastric cancer.

Gastric cancer (GC) is characterized by marked molecular heterogeneity that contributes to differential patient outcomes. Focal amplification in form of extrachromosomal DNA (ecDNA) is common in multiple cancer types and is associated with poor patient outcomes, but its prevalence and clinical implications in GC remain largely unclear. In this study, we analyzed whole genome and whole transcriptome sequencing from 76 GC patients collected at a single hospital (Seoul National University Bundang Hospital) in Korea. EcDNAs were detected in 22.4 % (n = 17) of GC patients. Notably, 75.0 % (n = 12) of the patients in the 'chromosomal instability (CIN)' category carried ecDNAs which frequently co-occurred with chromothripsis. We found that ecDNAs were enriched for known cancer genes, and the presence of ecDNAs was associated with poor patient prognosis. Among the CIN cases, patients carrying ecDNAs showed gene expression patterns related to chromosomal instability, as also observed in patients having only non-ecDNA chromosomal amplicons (ChAmp) but exhibited more pronounced immune suppression. Our findings show that ecDNAs display distinct molecular characteristics in GC, including the high prevalence of cancer genes and pronounced characteristic of immune suppression, alongside clinical implications, suggesting that ecDNA is a key molecular factor in the clinical management of GC patients, particularly for the CIN subtype patients.