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.

Three-dimensional genome structure and chromatin accessibility reorganization duringin vivoinduction of human T cell tolerance

“…The 3D genome interaction maps of CD4 + and CD8 + T cells were next investigated (Figure S3C-I) (Li et al, 2018; Wu et al, 2017). The switch of A/B compartments from steady-state T cells to tolerant ones is shown for chromosome 10 in Figure S3G.…”

Forces driving the three‐dimensional folding of eukaryotic genomes

“…On the basis of this new knowledge, whole‐genome conformation studies have been used to decipher how development or developmental disease (Dixon et al , ; Fraser et al , ; Lupiáñez et al , ; Franke et al , ; Bonev et al , ), cancer (Flavahan et al , ; Taberlay et al , ; Hnisz et al , ; Wu et al , ), DNA damage (Aymard et al , ; Canela et al , ), cellular aging (Criscione et al , ), and genetic variation (Javierre et al , ) impact on the structure and function of the genome. Needless to say that the advent of 3C technology (see overview in Denker & de Laat, ) has also provided insights into the higher order genomic organization of bacteria (e.g., Le & Laub, ; Lioy et al , ), fungi (e.g., Mizuguchi et al , ; Kim et al , ; Tanizawa et al , ), nematodes (e.g., Crane et al , ), the Plasmodium falciparum parasite (Ay et al , ), and plants (e.g., Dong et al , ).…”

Identification and Utilization of Copy Number Information for Correcting Hi-C Contact Map of Cancer Cell Line

“…It is well-established that chromatin contact map is highly influenced by the copy number events [15, 18]. Our analysis of Hi-C/3C-seq data demonstrated that interaction frequencies are positively correlated across cancer cell lines with the copy number tracks derived from the same cell line.…”

“…al. reported in multiple myeloma (MM) cells with whole/partial chromosomal gains/losses that copy number (CN)-amplified regions have higher interaction frequencies than CN-neutral (normal) regions [15]. They identified the TADs by insulation score method [6] using ICE-normalized interaction matrices [19] and found that the numbers of TADs increased by 25% and the average size of TADs decreases significantly compared to the normal B cells.…”