TY - JOUR
T1 - Diagnostic and Prognostic/Therapeutic Significance of Comprehensive Analysis of Bone and Soft Tissue Tumors Using Optical Genome Mapping and Next-Generation Sequencing
AU - Ghabrial, Jen
AU - Stinnett, Victoria
AU - Ribeiro, Efrain
AU - Klausner, Melanie
AU - Morsberger, Laura
AU - Long, Patty
AU - Middlezong, William
AU - Xian, Rena
AU - Gocke, Christopher
AU - Lin, Ming Tseh
AU - Rooper, Lisa
AU - Baraban, Ezra
AU - Argani, Pedram
AU - Pallavajjala, Aparna
AU - Murry, Jaclyn
AU - Gross, John M.
AU - Zou, Ying S.
N1 - Publisher Copyright:
© 2024 United States & Canadian Academy of Pathology
PY - 2025/4
Y1 - 2025/4
N2 - Detecting somatic structural variants (SVs), copy number variants (CNVs), and mutations in bone and soft tissue tumors is essential for accurately diagnosing, treating, and prognosticating outcomes. Optical genome mapping (OGM) holds promise to yield useful data on SVs and CNVs but requires fresh or snap-frozen tissues. This study aimed to evaluate the clinical utility of data from OGM compared with current standard-of-care cytogenetic testing. We evaluated 60 consecutive specimens from bone and soft tissue tumors using OGM and karyotyping, fluorescence in situ hybridization, gene fusion assays, and deep next-generation sequencing. OGM accurately identified diagnostic SVs/CNVs previously detected by karyotyping and fluorescence in situ hybridization (specificity = 100%). OGM identified diagnostic and pathogenic SVs/CNVs (∼23% of cases) undetected by karyotyping (cryptic/submicroscopic). OGM allowed the detection and further characterization of complex structural rearrangements including chromoanagenesis (27% of cases) and complex 3- to 6-way translocations (15% of cases). In addition to identifying 321 SVs and CNVs among cases with chromoanagenesis events, OGM identified approximately 9 SVs and 12 CNVs per sample. A combination of OGM and deep next-generation sequencing data identified diagnostic, disease-associated, and pathogenic SVs, CNVs, and mutations in ∼98% of the cases. Our cohort contained the most extensive collection of bone and soft tissue tumors profiled by OGM. OGM had excellent concordance with standard-of-care cytogenetic testing, detecting and assigning high-resolution genome-wide genomic abnormalities with higher sensitivity than routine testing. This is the first and largest study to provide insights into the clinical utility of combined OGM and deep sequencing for the pathologic diagnosis and potential prognostication of bone and soft tissue tumors in routine clinical practice.
AB - Detecting somatic structural variants (SVs), copy number variants (CNVs), and mutations in bone and soft tissue tumors is essential for accurately diagnosing, treating, and prognosticating outcomes. Optical genome mapping (OGM) holds promise to yield useful data on SVs and CNVs but requires fresh or snap-frozen tissues. This study aimed to evaluate the clinical utility of data from OGM compared with current standard-of-care cytogenetic testing. We evaluated 60 consecutive specimens from bone and soft tissue tumors using OGM and karyotyping, fluorescence in situ hybridization, gene fusion assays, and deep next-generation sequencing. OGM accurately identified diagnostic SVs/CNVs previously detected by karyotyping and fluorescence in situ hybridization (specificity = 100%). OGM identified diagnostic and pathogenic SVs/CNVs (∼23% of cases) undetected by karyotyping (cryptic/submicroscopic). OGM allowed the detection and further characterization of complex structural rearrangements including chromoanagenesis (27% of cases) and complex 3- to 6-way translocations (15% of cases). In addition to identifying 321 SVs and CNVs among cases with chromoanagenesis events, OGM identified approximately 9 SVs and 12 CNVs per sample. A combination of OGM and deep next-generation sequencing data identified diagnostic, disease-associated, and pathogenic SVs, CNVs, and mutations in ∼98% of the cases. Our cohort contained the most extensive collection of bone and soft tissue tumors profiled by OGM. OGM had excellent concordance with standard-of-care cytogenetic testing, detecting and assigning high-resolution genome-wide genomic abnormalities with higher sensitivity than routine testing. This is the first and largest study to provide insights into the clinical utility of combined OGM and deep sequencing for the pathologic diagnosis and potential prognostication of bone and soft tissue tumors in routine clinical practice.
KW - bone and soft tissue tumors
KW - copy number variants
KW - gene fusions
KW - mutations
KW - next-generation sequencing
KW - optical genome mapping
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U2 - 10.1016/j.modpat.2024.100684
DO - 10.1016/j.modpat.2024.100684
M3 - Article
C2 - 39675429
AN - SCOPUS:85214846212
SN - 0893-3952
VL - 38
JO - Modern Pathology
JF - Modern Pathology
IS - 4
M1 - 100684
ER -