【摘要】 目的 本研究旨在探讨染色质空间结构在正常核型和复杂核型这两类多发性骨髓瘤患者中的功能差异及其潜在影响。方法 本研究对1例1q21伴复杂核型和1例正常核型多发性骨髓瘤患者的浆细胞进行高通量染色体构象捕获(Hi-C)分析，解析两者在三维基因组结构的差异，并联合浆细胞的转录组特征，通过基因功能富集理解这些差异特征。结果 2个病例的36%染色质区室(compartment)发生了A/B转变(A/B switch),其中复杂核型的患者有1 041个基因发生B到A的转变。每个标本鉴定到3 500个左右的拓扑关联域(TAD),没有明显的差异；而复杂核型样鉴定的loop数量为1 069个，为正常样本的1/6,3种不同类型的loop在数量上也有明显差异，一定程度反应了其基因组稳定性的丧失。通过转录组分析显示两名患者在表达谱上也有很大差异，共鉴定6 150个差异表达基因(3 303个上调基因和2 847个下调基因)。结论 1q21复杂核型多发性骨髓瘤患者相较正常核型患者，浆细胞染色质不同层次的空间结构发生了较为明显的变化，从而引起基因的表达改变，激活癌症进展相关通路。更多还原

【Abstract】 Objective To investigate the functional differences and potential effects of chromatin spatial structure in patients with normal karyotype and complex karyotype multiple myeloma. Methods High-throughput chromosome conformational capture(Hi-C) analysis was performed on plasma cells of 1 case with 1q21 complex karyotype and 1 case with normal karyotype multiple myeloma, and the differences in three-dimensional genome structure between the two patients were analyzed, and the transcriptome characteristics of plasma cells were combined to investigate the differential features through gene functional enrichment. Results A/B switch occurred in 36% of the chromatin compartments in two cases, and 1 041 genes in patient with complex karyotype had B/A switch. About 3 500 topological association domains(TADs) were identified in each sample, and there was no significant difference. The number of loops identified in complex karyotype sample was 1 069, which was 1/6 of the normal sample, and there were significant differences in the number of three different types of loops, which to some extent reflected the loss of genome stability. Transcriptome analysis showed significant differences in expression profiles between the two patients, and a total of 6 150 differentially expressed genes(3 303 up-regulated genes and 2 847 down-regulated genes) were identified.Conclusion Compared with patient with normal karyotype, patient with 1q21 complex karyotype multiple myeloma exhibit significant changes in the spatial structure of plasma cell chromatin at different levels, which leads to changes in gene expression and activation of pathways related to cancer progression.更多还原