Structural Forms of ERBB2 Amplification and Their Clinical Significance in EAC Brain Metastases

We characterized the genomic architecture, evolutionary history, and tumor microenvironment of EAC brain metastases from 65 patients using whole-genome sequencing, single-cell spatial transcriptomics, and ERBB2 fluorescence in situ hybridization. We retrospectively identified patients who underwent neurosurgical resection for brain metastases arising from esophageal adenocarcinoma. Whole-genome sequencing was performed using a hybrid strategy that combined Oxford Nanopore long-read sequencing with Illumina short-read sequencing to enable high-resolution detection of copy number alterations and complex structural variants. This study identifies ERBB2 amplification as a dominant genomic feature of esophageal adenocarcinoma brain metastases and demonstrates that the structural organization of this amplicon is associated with clinical behavior.

• Type: Cancer Genomics
• Archive: European Genome-phenome Archive (EGA)