Advancements in Optical Genome Mapping Technology for Multiple Myeloma Management

Recent research highlights the effectiveness of optical genome mapping (OGM) technology in enhancing the diagnosis, prognosis, and treatment strategies for multiple myeloma, a prevalent form of blood cancer affecting plasma cells. The findings, published in The Journal of Molecular Diagnostics, showcase how OGM can develop a cytogenomic profile of tumors, making it suitable for standard practices in cytogenetics laboratories.

Multiple myeloma ranks as the second most common hematologic malignancy. While new therapeutic approaches have improved patient outcomes, including progression-free survival and overall quality of life, the disease remains largely incurable, particularly in cases where patients exhibit resistance to various treatments.

The conventional cytogenetic workflow for diagnosing multiple myeloma begins with tumor cell isolation, followed by established techniques such as fluorescent in situ hybridization (FISH). However, this method is often limited by low cell yields, which restricts the number of genetic markers that can be analyzed. Although high-throughput DNA sequencing requires fewer cells, it typically focuses on specific targets rather than providing a comprehensive analysis.

The study introduces an innovative strategy that leverages the OGM technique, which can identify structural and copy number variations across the entire genome in a single test. This advancement addresses the challenges associated with low cell quantities following sorting, allowing for a more thorough investigation.

The research team evaluated the OGM technique's feasibility in managing multiple myeloma and successfully reduced the cell count needed for effective analysis. They demonstrated that the method can be applied to samples diluted by up to 50%, achieving complete detection of clonal structural variants and copy number variants, with a detection threshold of at least 20% for copy number variants at this dilution.

In a small patient cohort, the OGM technique achieved a 93% concordance rate with the reference FISH method across five markers tested and identified over 22 additional genomic variations of clinical significance. This approach consolidates multiple analyses into a single test, reduces material requirements, and enhances prognostic accuracy for patients battling multiple myeloma.

The comprehensive nature of this technology, along with the ability to mix tumor and non-tumor cells, marks a significant innovation in the field. It enables the visualization of all genomic rearrangements and numerical abnormalities in a singular analysis, providing local laboratories and routine hospital settings with a robust detection capacity for multiple myeloma markers.

While it is important to note that OGM does not facilitate the detection of point mutations since it is not a sequencing method, the study indicates that targeted follow-up investigations for mutations in specific genes can be conducted using the same DNA sample extracted for OGM analysis. This eliminates the need for additional sample collection from the patient.

Integrating OGM into laboratory workflows is expected to enhance prognostic assessments and broaden therapeutic possibilities for multiple myeloma patients.