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.]]>
Inclusion Criteria: Adult patients receiving CD19 CAR T cell therapy as treatment for diffuse large B cell lymphoma (DLBCL) and variants Exclusion Criteria: Children under the age of 18]]>

我们对49例接受CD19靶向嵌合抗原受体（CAR-19）治疗的弥漫大B细胞淋巴瘤（DLBCL）患者的100份肿瘤及配对生殖系样本开展了全基因组测序（WGS）。研究发现，复杂结构变异、载脂蛋白B mRNA编辑酶催化多肽样（APOBEC）突变特征，以及活性氧诱导的基因组损伤，可预测CAR-19治疗耐药性。BAM格式文件将通过dbGaP数据库对外共享。
纳入标准：接受CD19 CAR-T细胞疗法治疗弥漫大B细胞淋巴瘤（DLBCL）的成年患者及变异携带者
排除标准：18岁以下儿童