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Single-Cell RNA Sequencing Study Finds Early Genomic Drivers of Multiple Myeloma

In a study appearing in Cancer Cell, researchers from MD Anderson Cancer Center identify early genomic drivers of malignant transformation of multiple myeloma. They performed single-cell RNA and B cell receptor sequencing of samples from 52 patients with myeloma precursors, which they compared to samples from people with multiple myeloma and healthy controls. "Integrating single-cell RNA sequencing and B cell receptor sequencing offers advantages for detecting clonal or aberrant plasma cells during the early stages of tumorigenesis," the authors write in their paper. They uncovered substantial genomic and transcriptional heterogeneity in the earliest precursor stages of the disease, and additionally found that the intratumoral heterogeneity extends to established myeloma-related genes, such as CCND1CD38BCMALAMP5, and MYC. The researchers further integrated fluorescence in situ hybridization along with single-cell sequencing data, which helped overcome the limitation of low tumor purity in the precursor stage to identify genetic abnormalities in multiple myeloma precursors. "These findings add to our knowledge about myeloma precursor disease progression, providing valuable insights into patient risk stratification, biomarker discovery, and possible clinical application," the authors write.