Purpose: Whole-genome sequencing (WGS) of patients with newly diagnosed multiple myeloma (NDMM) has shown recurrent structural variant (SV) involvement in distinct regions of the genome (i.e., hotspots) and causing recurrent copy-number alterations. Together with canonical immunoglobulin translocations, these SVs are recognized as "recurrent SVs." More than half of SVs were not involved in recurrent events. The significance of these "rare SVs" has not been previously examined.
Experimental Design: In this study, we utilize 752 WGS and 591 RNA sequencing data from patients with NDMM to determine the role of rare SVs in myeloma pathogenesis.
Results: Ninety-four percent of patients harbored at least one rare SV event. Rare SVs showed an SV class-specific enrichment within genes and superenhancers associated with outlier gene expression. Furthermore, known myeloma driver genes recurrently impacted by point mutations were dysregulated by rare SVs.
Conclusions: Overall, we demonstrate the association of rare SVs with aberrant gene expression supporting a potential driver role in myeloma pathogenesis.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10841766 | PMC |
| http://dx.doi.org/10.1158/1078-0432.CCR-23-1045 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Structural variations (SVs) play important roles in genetic diversity, evolution, and carcinogenesis and are, as such, important for human health. However, it remains unclear how spatial proximity of double-strand breaks (DSBs) affects the formation of SVs. To investigate if spatial proximity between two DSBs affects DNA repair, we used data from 3C experiments (Hi-C, ChIA-PET, and ChIP-seq) to identify highly interacting loci on six different chromosomes.
View Article and Find Full Text PDFAcute Arterial Ischemia Secondary to Intrapelvic Acetabular Migration: A Multidisciplinary Approach.
Cureus
December 2024
Vascular Surgery, Centro Médico Nacional 20 de Noviembre, Mexico City, MEX.
This case report evaluates current diagnostic and treatment approaches for intrapelvic acetabular migration, focusing on the rare but serious complication of acute limb ischemia following hip arthroplasty. A 67-year-old female with a history of total hip arthroplasty 10 years ago presented with acute limb ischemia after experiencing a traumatic event 72 hours prior, which had caused displacement of her hip prosthesis. Notably, she had a history of a traumatic event two years earlier for which she had been advised to undergo surgical correction, which she had refused.
View Article and Find Full Text PDFRare germline structural variants increase risk for pediatric solid tumors.
Science
January 2025
Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Pediatric solid tumors are a leading cause of childhood disease mortality. In this work, we examined germline structural variants (SVs) as risk factors for pediatric extracranial solid tumors using germline genome sequencing of 1765 affected children, their 943 unaffected parents, and 6665 adult controls. We discovered a sex-biased association between very large (>1 megabase) germline chromosomal abnormalities and increased risk of solid tumors in male children.
View Article and Find Full Text PDFHaplotype-Resolved Genotyping and Association Analysis of 1,020 β-Thalassemia Patients by Targeted Long-Read Sequencing.
Adv Sci (Weinh)
December 2024
Innovation Center for Diagnostics and Treatment of Thalassemia, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Despite the well-documented mutation spectra of β-thalassemia, the genetic variants and haplotypes of globin gene clusters modulating its clinical heterogeneity remain incompletely illustrated. Here, a targeted long-read sequencing (T-LRS) is demonstrated to capture 20 genes/loci in 1,020 β-thalassemia patients. This panel permits not only identification of thalassemia mutations at 100% of sensitivity and specificity, but also detection of rare structural variants (SVs) and single nucleotide variants (SNVs) in modifier genes/loci.
View Article and Find Full Text PDFUniVar: A variant interpretation platform enhancing rare disease diagnosis through robust filtering and unified analysis of SNV, INDEL, CNV and SV.
Comput Biol Med
December 2024
Hong Kong Genome Institute, Hong Kong Science Park, Shatin, Hong Kong, China; Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China; Laboratory of Computational Genomics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China. Electronic address:
Background: Interpreting the pathogenicity of genetic variants associated with rare diseases is a laborious and time-consuming endeavour. To streamline the diagnostic process and lighten the burden of variant interpretation, it is crucial to automate variant annotation and prioritization. Unfortunately, currently available variant interpretation tools lack a unified and comprehensive workflow that can collectively assess the clinical significance of these types of variants together: small nucleotide variants (SNVs), small insertions/deletions (INDELs), copy number variants (CNVs) and structural variants (SVs).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!