{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Li YP"],"funding":["Natural Science Foundation of Beijing Municipality","National Natural Science Foundation of China"],"pagination":["pgac162"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9802398"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["1(4)"],"pubmed_abstract":["Retinoblastoma (Rb) is a type of malignant tumor due to abnormal retinogenesis with biallelic mutations of the <i>RB1</i> 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 <i>RB1</i> mutations. To obtain straightforward evidence for this hypothesis, we investigated whether two-hit mutations of the <i>RB1</i> 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 (<i>RB1<sup>m1/</sup> <sup>wt</sup></i> ) from a Rb patient. A second-allele <i>RB1</i> gene mutat"],"journal":["PNAS nexus"],"pubmed_title":["Second hit impels oncogenesis of retinoblastoma in patient-induced pluripotent stem cell-derived retinal organoids: direct evidence for Knudson's theory."],"pmcid":["PMC9802398"],"funding_grant_id":["81970838","Z200014","82171470","82125007"],"pubmed_authors":["Shen RJ","Li YP","Zhang X","Wang YT","Jin ZB","Wang W","Jin LW","Jin K"],"additional_accession":[]},"is_claimable":false,"name":"Second hit impels oncogenesis of retinoblastoma in patient-induced pluripotent stem cell-derived retinal organoids: direct evidence for Knudson's theory.","description":"Retinoblastoma (Rb) is a type of malignant tumor due to abnormal retinogenesis with biallelic mutations of the <i>RB1</i> 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 <i>RB1</i> mutations. To obtain straightforward evidence for this hypothesis, we investigated whether two-hit mutations of the <i>RB1</i> 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 (<i>RB1<sup>m1/</sup> <sup>wt</sup></i> ) from a Rb patient. A second-allele <i>RB1</i> gene mutat","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Sep","modification":"2026-07-09T13:22:13.134Z","creation":"2025-04-06T18:02:50.284Z"},"accession":"S-EPMC9802398","cross_references":{"pubmed":["36714839"],"doi":["10.1093/pnasnexus/pgac162"]}}