A CHOP-led team presented evidence of a brain tumor linked to rare adeno-associated virus (AAV) integration, highlighting a potential long-term risk to the AAV gene therapy field. The case, presented at ASGCT and published in the New England Journal of Medicine, involved a 5-year-old boy with severe MPS I deficiency who later developed a PLAG1-driven neuroepithelial tumor after intracisternal magna delivery of an AAV9 vector carrying IDUA. RNA sequencing found a fusion consistent with AAV9 cassette integration to PLAG1. Investigators reported successful tumor removal and no signs of growth eight months post-surgery, while the presentation framed the episode as a signal to strengthen long-term monitoring and deepen understanding of integration-related events.