Comparative Analysis of Targeted RNA-Seq and Optical Genome Mapping for Detecting Gene Rearrangements in Acute
Chi Young Ok1, Guilin Tang1, Sanam Loghavi1
1Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cancers
|November 13, 2025
Summary
Targeted RNA sequencing and Optical Genome Mapping (OGM) are complementary tools for acute leukemia diagnosis. While RNA-Seq excels at detecting fusion transcripts, OGM is superior for identifying enhancer-hijacking events, with both methods offering unique insights into gene rearrangements.
Area of Science:
- Hematology and Oncology
- Genomics and Molecular Diagnostics
- Cancer Genetics
Background:
- Gene rearrangements in oncogenes are critical drivers of acute leukemia, impacting classification, prognosis, and treatment.
- Targeted RNA sequencing (RNA-Seq) panels are increasingly utilized for detecting gene fusions in diagnostics.
- Comparative evaluations of RNA-Seq with orthogonal technologies like Optical Genome Mapping (OGM) are limited.
Purpose of the Study:
- To compare the diagnostic performance of a 108-gene anchored multiplex PCR (AMP)-based RNA-Seq panel against Optical Genome Mapping (OGM).
- To evaluate the concordance and unique detection capabilities of both RNA-Seq and OGM in a large cohort of acute leukemia cases.
Main Methods:
- A comparative study involving 467 acute leukemia patients (360 AML, 89 B-ALL, 12 T-ALL, 6 MPAL).
- Performance evaluation of a 108-gene AMP-based RNA-Seq panel versus Optical Genome Mapping (OGM).
- Analysis of concordance rates, unique findings, and specific aberration types (e.g., enhancer-hijacking, deletions).
Main Results:
- Overall concordance between RNA-Seq and OGM was 74.7% for 234 detected gene/rearrangement fusions, with significant variation across leukemia types (80.2% in B-ALL vs. 41.7% in T-ALL).
- OGM uniquely identified 15.8% of rearrangements, while RNA-Seq exclusively identified 9.4%.
- Enhancer-hijacking events showed markedly lower concordance (20.6%) compared to other aberrations (93.1%). OGM detected these events effectively, while RNA-Seq identified some deletions as simple deletions rather than rearrangements.
Conclusions:
- Targeted RNA-Seq is effective for detecting chimeric fusion transcripts and slightly better for identifying deletion-driven fusions.
- Optical Genome Mapping (OGM) is superior for detecting enhancer-hijacking events that do not produce fusion transcripts.
- Both RNA-Seq and OGM are complementary diagnostic tools for comprehensive workup of acute leukemia cases.
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