Identification of Somatic Structural Variants in Solid Tumors by Optical Genome Mapping

Area of Science:

• Genomics
• Cancer Biology
• Molecular Diagnostics

Background:

• Somatic structural variants (SVs) are key drivers of cancer, but standard sequencing methods struggle to detect them.
• Optical genome mapping (OGM) excels at identifying large and complex SVs but requires ultra-high-molecular-weight DNA.

Purpose of the Study:

• To establish and validate a robust protocol for extracting high-molecular-weight DNA from solid tumors for OGM.
• To assess the utility of OGM in detecting clinically relevant somatic SVs across diverse solid tumor types.

Main Methods:

• Development and application of a paramagnetic nanobind disc-based protocol for DNA extraction from solid tumor tissues (as little as 6.5 mg).
• Performance of Optical Genome Mapping (OGM) on extracted DNA to generate genome maps.
• Identification and analysis of somatic SVs, with filtering against the GRCh38 human reference genome.

Main Results:

• Successful extraction of high-molecular-weight DNA from various solid tumors, yielding high map rates and effective OGM coverage.
• Identification of somatic SVs impacting cancer-related genes in all tested samples.
• Demonstrated high positive and negative predictive values for somatic SV detection using GRCh38 filtering, alongside evidence of intra-sample heterogeneity.

Conclusions:

• The developed DNA extraction protocol is effective for OGM across diverse solid tumors.
• OGM combined with SV analysis provides comprehensive genome-wide detection of functionally important SVs in cancer.
• This approach holds significant potential for cancer prognosis and treatment strategy development.