Second hit impels oncogenesis of retinoblastoma in patient-induced pluripotent stem cell-derived retinal organoids: direct evidence for Knudson's theory.

ABSTRACT: Retinoblastoma (Rb) is a type of malignant tumor due to abnormal retinogenesis with biallelic mutations of the RB1 gene. Its pathogenesis has been proposed as a "two-mutation hypothesis" by Knudson since 1971; however, there remain some debates on disease onset sufficiency of the biallelic RB1 mutations. To obtain straightforward evidence for this hypothesis, we investigated whether two-hit mutations of the RB1 gene drive tumorigenesis in patient-induced pluripotent stem cell (hiPSC)-derived human retinal organoids (hROs) and whether single allelic mutation hiPSC-derived hROs exhibit molecular and cellular defects. We generated hiPSCs with a heterozygous germline mutation (RB1^{m1/ wt} ) from a Rb patient. A second-allele RB1 gene mutat

SUBMITTER: Li YP 

PROVIDER: S-EPMC9802398 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature