Application of Ultrasensitive Chromosomal Aneuploidy Detection (UCAD) as a Surrogate Biomarker of Minimal Residual Diseases for Multiple Myeloma Patients

In multiple myeloma, Minimal Residual Disease (MRD) refers to myeloma cells that are present in the bone marrow after a clinical response has been measured and the patient is in remission. A patient who tests "MRD negative" after treatment for myeloma has less than one myeloma cell per million bone marrow cells. Data from recent clinical trials suggest that patients with such a low level of disease may be less likely to experience a relapse of their condition than patients with higher levels. In recent years, MRD testing is now be applied in the management of patients receiving standard therapies for the disease.

Chromosomal instability(CIN) results from errors in chromosome segregation during mitosis, leading to structural and numerical chromosomal abnormalities. It will generate genomic heterogeneity that acts as a substrate for natural selection. Furthermore, it is proved that tumors with aneuploidies and polyploidy resulting from whole-genome doubling are related with metastasis, treatment resistance, and decreased overall survival. It is estimated that 60%-80% of human tumors exhibit chromosomal abnormalities suggestive of CIN. CIN positively correlates with tumor stage and is enriched in relapsed as well as metastatic tumor specimens. Due to the ubiquity of CIN in cancer cells and cancer cell releasing DNA into peripheral blood (PB) when apoptosis, it is a potentially non-invasive way to detect CIN in PB cfDNA from the MM patients to character MRD level. UCAD is a new method to detecting CIN in the DNA sample from patients, including extracting cfDNA from PB, analyzing DNA by low-coverage whole-genome sequencing, processing the data by bio-information techniques, and finally optimizing the management of MM patients.