Characterization of retrocopies in 663 individuals with esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is a common gastrointestinal malignancy with partially known etiology. Previous studies have proved the essential role of structural variations (SVs) in ESCC; however, the contribution of retrocopies, a rare form of SV mediated by the L1 retrotransposition and often neglected by the routine SV pipeline, remains unclear. In this study, we applied multi-omics data of 663 pairs of ESCC tumor-normal samples to generate a comprehensive spectrum of retrocopies on ESCC. Generally, worse overall survival of patients who carried retrocopies involving cancer-associated genes suggested a role of retrocopies in ESCC. The enrichment of parent genes in ribosome biogenesis and mitochondrial respiration chain suggested a potential role in energetic modulation. Additionally, the characterization of insertion sites revealed the regulatory function of retrocopies in ESCC. Overall, this study suggests the need to characterize retrocopies in cancer studies, and the comprehensive landscape of retrocopies extends the current understanding of ESCC etiology.