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Whole-Genome Sequencing Reveals Complex Genomic Features Underlying Anti-CD19 CAR T-Cell Treatment Failure in Lymphoma

We performed Whole-Genome Sequencing (WGS) on 100 tumor and matched germline samples from 49 CD19-directed chimeric antigen receptor (CAR-19)-treated diffuse large B cell lymphoma (DLBCL) patients. We found that the presence of complex structural variants, APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide) mutational signatures, and genomic damage from reactive oxygen species predict CAR-19 resistance. BAM files will be available through dbGaP.