Optical Genome Mapping Reveals Novel Structural Variants in Lymphoblastic Lymphoma

Area of Science:

• Genomics
• Pediatric Oncology
• Molecular Diagnostics

Background:

• Accurate diagnosis of pediatric lymphoblastic lymphoma (LBL) is crucial for pathogenesis studies.
• Conventional cytogenomic testing has limitations in resolution, throughput, and identifying complex genomic rearrangements.
• Optical genome mapping (OGM) offers an all-in-one solution for detecting major genomic risk markers.

Purpose of the Study:

• To investigate the cytogenetics of pediatric LBL patients using OGM.
• To evaluate the capability of OGM in identifying genomic aberrations in LBL.
• To compare OGM findings with conventional cytogenetic techniques.

Main Methods:

• Five pediatric LBL samples were analyzed using OGM.
• Whole-exon sequencing (WES) confirmed structural variants (SVs) identified by OGM.
• cDNA-based PCR validated fusion mRNA, such as HBS1L::AHI1.

Main Results:

• OGM identified 251 rare variants and 229 copy number variants.
• OGM detected more pathologically significant SVs than traditional methods.
• Two novel fusion genes, HBS1L::AHI1 and GRIK1::NSDHL, were discovered and confirmed.

Conclusions:

• OGM is feasible for detecting genomic aberrations in pediatric LBL.
• These aberrations may be important driving factors in lymphomagenesis.
• OGM enhances the detection of clinically relevant genomic alterations in LBL.