Impact of rare structural variant events in newly diagnosed multiple myeloma Journal Article

   


Authors: Chojnacka, M.; Diamond, B.; Ziccheddu, B.; Rustad, E.; Maclachlan, K.; Papadimitriou, M.; Boyle, E. M.; Blaney, P.; Usmani, S.; Morgan, G.; Landgren, O.; Maura, F.
Article Title: Impact of rare structural variant events in newly diagnosed multiple myeloma
Abstract: 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. ©2023 American Association for Cancer Research.
Keywords: signal transduction; human tissue; gene translocation; major clinical study; gene deletion; genetics; pathogenesis; multiple myeloma; gene expression; cohort analysis; genetic variability; cytogenetics; rna; oncogene; gene rearrangement; bone marrow biopsy; human genome; gene duplication; translocation, genetic; genome; point mutation; cyclin d1; genome, human; dna copy number variations; cyclin d2; cyclin d3; copy number variation; ccnd2 gene; chromothripsis; ccnd1 gene; humans; human; article; whole genome sequencing; rna sequencing; transcription factor mafa; transcription factor mafb; chromoplexy; structural variant; ccnd3 gene; mafa gene; mafb gene; nsd2 gene
Journal Title: Clinical Cancer Research
Volume: 30
Issue: 3
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2024-02-01
Start Page: 575
End Page: 585
Language: English
DOI: 10.1158/1078-0432.Ccr-23-1045
PUBMED: 37939148
PROVIDER: scopus
PMCID: PMC10841766
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85183394032&doi=10.1158%2f1078-0432.CCR-23-1045&partnerID=40&md5=11a011963e55b93f571477da08140970
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- Source: Scopus
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MSK Authors
  1. Kylee Maclachlan
    143 Maclachlan
  2. Saad Zafar Usmani
    296 Usmani
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