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December 8, 2025BloodOpen Access

Multiomic evidence of coordinated complex rearrangements, enhancer hijacking, and epigenomic signatures in the first whole-chromosome-phased myeloma genomes

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Authors

NBNathan BeckerZSZachary SanbornJHJames E. Hoffman

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Overview

Genomic architecture shows structural variation and DNA methylation in multiple myeloma, highlighting complex proto-oncogene interactions.

Key Points

  • To generate chromosome-scale haplotype-resolved genomes in multiple myeloma and integrate them with epigenetic states.
  • Utilized multiple myeloma patient-derived xenografts for multiomic data generation.
  • Conducted short-read (Illumina) and long-read (PacBio) whole genome sequencing.
  • Identified single nucleotide variations, copy number abnormalities, structural variations, and expression patterns.
  • Integrated epigenetic data such as DNA methylation and chromatin states for analysis.
  • Achieved 96.3% haplotype phasing on average per autosome across genomes.
  • Defined complex structural variations including t(11;14) and others impacting genome organization and epigenetic regulation.
  • Demonstrated over-expression of proto-oncogene SKIL linked with hypomethylated regions surrounding translocation breakpoints.

Cite This Study

Becker et al. (2025) studied this question.

synapsesocial.com/papers/69362f444fa91c937236d5fchttps://doi.org/10.1182/blood-2025-3928
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Abstract 5940: Chromosome-level phasing to resolve haplotypes using multiomic data in multiple myeloma reveals complex distal interactions between chromosomes that impacts epigenetic states and gene expression2026
  2. 2Single-cell DNA sequencing uncovers synergistic co-mutations in multiple myeloma2025
  3. 3Abstract 3248: Characterization of multiple myeloma genomes with LinkPrep assay enables detection of somatic variation and SV-driven interactions of the 3D genome2026
  4. 4Abstract 4406: Single cell multiomic analysis reveals how genomic, epigenomic and transcriptomic events drive progression of multiple myeloma precursor states2024
  5. 5Supplementary Figure S7 from Multiomic mapping of acquired chromosome 1 copy number and structural variants to identify therapeutic vulnerabilities in multiple myeloma.2024