The challenges of assessing the clinical risk of oncogenesis are illustrated by the early gamma (γ)-RV-based hematopoietic stem cell gene therapy trials for X-linked severe combined immunodeficiency (SCID-X1), Wiskott-Aldrich syndrome (WAS), chronic granulomatous disease (CGD), and adenosine deaminase (ADA-SCID). This evidence concerns the gene ADA and chronic granulomatous disease.