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Aberrant EGFR activation is observed in over 50% of cases of adult glioblastoma (GBM). Nevertheless, EGFR antibodies are ineffective in clinical GBM treatment, suggesting the existence of redundant EGFR activation mechanisms. Whether circular RNA (circRNA) encodes a protein involved in EGFR-driven GBM remains unclear. We reported an unexpected mechanism in which circular EGFR RNA (circ-EGFR) encodes a novel EGFR variant to sustained EGFR activation. We used RNA-seq, Northern blot and Sanger sequencing to confirm the existence of circ-EG