3D genome of multiple myeloma reveals spatial genome disorganization associated with copy number variations.

Abstract

The Hi-C method is widely used to study the functional roles of the three-dimensional (3D) architecture of genomes. Here, we integrate Hi-C, whole-genome sequencing (WGS) and RNA-seq to study the 3D genome architecture of multiple myeloma (MM) and how it associates with genomic variation and gene expression. Our results show that Hi-C interaction matrices are biased by copy number variations (CNVs) and can be used to detect CNVs. Also, combining Hi-C and WGS data can improve the detection of translocations. We find that CNV breakpoints significantly overlap with topologically associating domain (TAD) boundaries. Compared to normal B cells, the numbers of TADs increases by 25% in MM, the average size of TADs is smaller, and about 20% of genomic regions switch their chromatin A/B compartment types. In summary, we report a 3D genome interaction map of aneuploid MM cells and reveal the relationship among CNVs, translocations, 3D genome reorganization, and gene expression regulation.

• Authors: Pengze Wu, Tingting Li, Ruifeng Li, Lumeng Jia, Ping Zhu, Yifang Liu, Qing Chen, Daiwei Tang, Yuezhou Yu, Cheng Li
• Journal: Nature communications (Nat Commun) Vol. 8 Issue 1 Pg. 1937 (12 05 2017) ISSN: 2041-1723 [Electronic] England
• PMID: 29203764 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chromatin

Topics

• B-Lymphocytes
• Cell Line, Tumor
• Chromatin (genetics)
• Chromosome Mapping
• DNA Copy Number Variations (genetics)
• Gene Expression
• Gene Expression Regulation, Neoplastic (genetics)
• Genome (genetics)
• High-Throughput Nucleotide Sequencing
• Humans
• Molecular Conformation
• Multiple Myeloma (genetics)
• Nucleic Acid Conformation
• Whole Genome Sequencing