Loss of SYNCRIP unleashes APOBEC-driven mutagenesis, tumor heterogeneity, and AR-targeted therapy resistance in prostate cancer
Li X, Wang Y, Deng S, Zhu G, Wang C, Johnson N, Zhang Z, Tirado C, Xu Y, Metang L, Gonzalez J, Mukherji A, Ye J, Yang Y, Peng W, Tang Y, Hofstad M, Xie Z, Yoon H, Chen L, Liu X, Chen S, Zhu H, Strand D, Liang H, Raj G, He H, Mendell J, Li B, Wang T, Mu P. Loss of SYNCRIP unleashes APOBEC-driven mutagenesis, tumor heterogeneity, and AR-targeted therapy resistance in prostate cancer. Cancer Cell 2023, 41: 1427-1449.e12. PMID: 37478850, PMCID: PMC10530398, DOI: 10.1016/j.ccell.2023.06.010.Peer-Reviewed Original ResearchConceptsProstate cancerTherapy resistanceTumor heterogeneityTumor mutational burdenCell-intrinsic mechanismsPromote tumor heterogeneityMutational burdenTargeted therapyDriver mutationsPCa cellsCancer cellsHuman cancersMutated genesCancerMutational signaturesProstateTumorTherapyFOXA1APOBEC proteinsAPOBEC3BEP300Molecular brakeMutationsSYNCRIPAbstract 93: An endogenous molecular brake preventing APOBEC-driven tumor mutational burden, heterogeneity and therapy resistance
Mu P, Li X, Wang Y, Wang T, Deng S. Abstract 93: An endogenous molecular brake preventing APOBEC-driven tumor mutational burden, heterogeneity and therapy resistance. Cancer Research 2023, 83: 93-93. DOI: 10.1158/1538-7445.am2023-93.Peer-Reviewed Original ResearchTumor mutational burdenTherapy resistanceMutational burdenMolecular brakeSingle cell RNA-seqDriver mutationsDrivers of mutagenesisAmerican Association for Cancer Research annual meetingsClinical outcomes of patientsCRISPR library screensRNA-seqExome-sequencingScRNA-seqOutcomes of patientsLibrary screeningFunctional screeningNon-malignant cellsCell-intrinsic mechanismsPromote heterogeneityMutagenesisMutated genesAPOBEC proteinsMutational signaturesMutationsPotential therapeutic target
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