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Optical Genome Mapping versus Whole-Genome Sequencing in the Clinical Diagnosis of Gynecologic Mesenchymal Tumors

Wallander, Karin ; Lin, Yingbo ; Ivanchuk, Vadym ; Difilippo, Valeria LU ; Chellappa, Venkatesh ; Murugan, Sarath K. ; Öfverholm, Ingegerd ; Bränström, Robert ; Nord, Karolin H. LU and Carlson, Joseph , et al. (2026) In Journal of Molecular Diagnostics 28(2). p.187-198
Abstract

Optical genome mapping (OGM) enables high-resolution detection of structural variants (SVs) and copy number aberrations (CNAs) using ultralong DNA molecules and minimal bioinformatics processing. Its diagnostic utility in solid tumors remains underexplored. Whole-genome sequencing (WGS) offers comprehensive variant detection but is resource intensive. This study presents a technical benchmarking of OGM versus WGS for mesenchymal tumors of the gynecologic tract. Twenty-five uterine mesenchymal tumors were prospectively analyzed using matched WGS, transcriptome sequencing, and OGM. Detected SVs, CNAs, and fusion genes were compared across platforms. OGM identified structural driver events in 80% of cases and demonstrated high concordance... (More)

Optical genome mapping (OGM) enables high-resolution detection of structural variants (SVs) and copy number aberrations (CNAs) using ultralong DNA molecules and minimal bioinformatics processing. Its diagnostic utility in solid tumors remains underexplored. Whole-genome sequencing (WGS) offers comprehensive variant detection but is resource intensive. This study presents a technical benchmarking of OGM versus WGS for mesenchymal tumors of the gynecologic tract. Twenty-five uterine mesenchymal tumors were prospectively analyzed using matched WGS, transcriptome sequencing, and OGM. Detected SVs, CNAs, and fusion genes were compared across platforms. OGM identified structural driver events in 80% of cases and demonstrated high concordance with WGS for major CNAs and translocations. In select cases, OGM resolved complex rearrangements not clearly defined by WGS, including a PLAG1 :: RERE fusion and an embedded inversion in a RAD51B :: HMGA2 event. Conversely, WGS uniquely detected a truncating NF1 translocation and a TSC2 :: SENP3 fusion, both clinically significant. OGM is a technically robust platform for SV and CNA detection in mesenchymal tumors, and it may serve as an efficient alternative to sequencing-based cytogenomic approaches in selected clinical contexts, especially in tumors known to be driven by gross chromosomal rearrangements. WGS provides a comprehensive view of the cancer genome, suitable for tumors driven by single-nucleotide variants, SVs, and CNAs. The choice between platforms should be guided by clinical context, diagnostic needs, and available resources.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Molecular Diagnostics
volume
28
issue
2
pages
12 pages
publisher
Elsevier
external identifiers
  • scopus:105027963752
  • pmid:41320126
ISSN
1525-1578
DOI
10.1016/j.jmoldx.2025.11.003
language
English
LU publication?
yes
id
2bcc1e08-cd4b-48d3-8c85-99dc687b6e29
date added to LUP
2026-02-19 12:14:37
date last changed
2026-04-16 22:02:10
@article{2bcc1e08-cd4b-48d3-8c85-99dc687b6e29,
  abstract     = {{<p>Optical genome mapping (OGM) enables high-resolution detection of structural variants (SVs) and copy number aberrations (CNAs) using ultralong DNA molecules and minimal bioinformatics processing. Its diagnostic utility in solid tumors remains underexplored. Whole-genome sequencing (WGS) offers comprehensive variant detection but is resource intensive. This study presents a technical benchmarking of OGM versus WGS for mesenchymal tumors of the gynecologic tract. Twenty-five uterine mesenchymal tumors were prospectively analyzed using matched WGS, transcriptome sequencing, and OGM. Detected SVs, CNAs, and fusion genes were compared across platforms. OGM identified structural driver events in 80% of cases and demonstrated high concordance with WGS for major CNAs and translocations. In select cases, OGM resolved complex rearrangements not clearly defined by WGS, including a PLAG1 :: RERE fusion and an embedded inversion in a RAD51B :: HMGA2 event. Conversely, WGS uniquely detected a truncating NF1 translocation and a TSC2 :: SENP3 fusion, both clinically significant. OGM is a technically robust platform for SV and CNA detection in mesenchymal tumors, and it may serve as an efficient alternative to sequencing-based cytogenomic approaches in selected clinical contexts, especially in tumors known to be driven by gross chromosomal rearrangements. WGS provides a comprehensive view of the cancer genome, suitable for tumors driven by single-nucleotide variants, SVs, and CNAs. The choice between platforms should be guided by clinical context, diagnostic needs, and available resources.</p>}},
  author       = {{Wallander, Karin and Lin, Yingbo and Ivanchuk, Vadym and Difilippo, Valeria and Chellappa, Venkatesh and Murugan, Sarath K. and Öfverholm, Ingegerd and Bränström, Robert and Nord, Karolin H. and Carlson, Joseph and Haglund de Flon, Felix}},
  issn         = {{1525-1578}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{187--198}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Molecular Diagnostics}},
  title        = {{Optical Genome Mapping versus Whole-Genome Sequencing in the Clinical Diagnosis of Gynecologic Mesenchymal Tumors}},
  url          = {{http://dx.doi.org/10.1016/j.jmoldx.2025.11.003}},
  doi          = {{10.1016/j.jmoldx.2025.11.003}},
  volume       = {{28}},
  year         = {{2026}},
}