Three-dimensional genomic characterization of two multiple myeloma patients with normal karyotype and complex karyotype
Objective To investigate the functional differences and potential effects of chromatin spatial structure in pa-tients with normal karyotype and complex karyotype multiple myeloma. Methods High-throughput chromosome conforma-tional 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 ana-lyzed,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 1041 genes in patient with complex karyotype had B/A switch. About 3500 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 1069,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 6150 differentially expressed genes (3303 up-regulated genes and 2847 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 dif-ferent levels,which leads to changes in gene expression and activation of pathways related to cancer progression.
万方数据
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