Optical genome mapping technology shows promise for diagnosis, prognosis and therapeutic options of multiple myeloma

Researchers have demonstrated the potential of the innovative optical genome mapping (OGM) technique for the diagnosis, prognosis, and therapeutic management of multiple myeloma. This new study in The Journal of Molecular Diagnostics, details how this novel method can establish the cytogenomic profile of the tumor on a scale suitable for routine practice in cytogenetics laboratories.

Multiple myeloma, a type of blood cancer that forms in plasma cells (a type of white blood cells), is the second most common hematologic malignancy. Over the past few decades, the introduction of novel therapies has significantly improved progression-free survival and overall survival, with less toxicity and an improved quality of life. Nevertheless, the disease remains largely incurable with poor outcomes, especially among patients resistant to multiple drug classes.

Cytogenetic gold standard workflow in multiple myeloma first starts with the isolation of tumor cells, which is an essential prerequisite, followed by traditional routine techniques (fluorescent in situ hybridization, “FISH”). However, cell sorting often limits the number of markers that can be investigated due to low cell yields. Even though some other techniques such as high throughput DNA sequencing require fewer cells, the search for markers remains targeted and not exhaustive.

This study presents an innovative approach combining the cutting-edge OGM technique, capable of identifying structural variants and copy number variations across the entire genome on a single test with the mix of tumor and non-tumor fraction for each patient to overcome the issue of low cell amount after cell sorting.

Lead investigator Agnès Daudignon, Ph.D., Institute of Medical Genetics, Lille University Hospital, and Hematology and Immunology Laboratory, Valenciennes University Hospital (France), explains, “We wanted to test the feasibility of OGM in the genetic management of multiple myeloma to establish the cytogenomic profile of the tumor on a scale suitable for routine practice in cytogenetics laboratories.”

Investigators tested the OGM technique and confirmed the possibility of reducing the number of cells required. They demonstrated that the technique can be applied to pure sorted samples diluted up to 50% for complete detection of clonal structural variants and copy number variants, with a detection threshold of at least 20% for copy number variants at 50%.

Analysis of a small series of patients showed a 93% concordance with the reference FISH technique on five tested markers and allowed the identification of more than 22 additional genomic variations of interest. This method streamlines several analyses into a single test, reduces material requirements, and improves prognostic stratification for patients with multiple myeloma.

The pan-genomic nature of this technology, combined with the concept of mixing tumor and non-tumor cells, makes this research particularly innovative. It allows for the visualization of all rearrangements and numerical anomalies of the samples in a single layer, providing local laboratories and/or routine hospital settings with an excellent level of detection of multiple myeloma markers, which could be described as pan-genomic technology on a human scale.

Dr. Daudignon concludes, “Of course, this technology does not allow for the detection of point mutations in genes, since it is not a sequencing technique. However, we have demonstrated that targeted complementary research for mutations on certain genes of interest can be performed using the same DNA sample extracted for the OGM, meaning there is no need to collect a new sample from the patient.

“Our research shows that integrating OGM into laboratory workflows would enhance prognostic stratification and expand therapeutic options.”