FAM46C-mediated tumor heterogeneity predicts extramedullary metastasis and poorer survival in multiple myeloma

Cancers originate from a single cell according to Nowell's theory of clonal evolution. The enrichment of the most aggressive clones has been developed and the heterogeneity arises for genomic instability and environmental selection. Multiple myeloma (MM) is a multiple relapse plasma cell cancer generated from bone marrow. Although there were accumulating researches in multiple myeloma pathogenesis, the heterogeneity remains poorly understood. The participants enrolled in this study were 4 EMP+ (EMP, Extramedullary plasmacytoma) and 2 EMP-primarily untreated MM patients. Single cell RNA sequencing and analysis were conducted for the single cell suspension, which was sorted by flow cytometry from peripheral blood mononuclear cells or bone marrow cells. In our research, the results of single cell RNA sequencing show that FAM46C determines MM tumor heterogeneity predicting extramedullary metastasis by influencing RNA stability. Further, we integrated and analyzed 2280 multiple myeloma samples from 7 independent datasets, which uncover that FAM46C mediated tumor heterogeneity predicts poorer survival in multiple myeloma.

Automated summary

According to Nowell's theory of clonal evolution, cancers originate from a single cell. The enrichment of aggressive clones and the heterogeneity of tumors are caused by genomic instability and environmental selection. Multiple myeloma is a relapse plasma cell cancer generated from bone marrow. Despite previous research on multiple myeloma pathogenesis, heterogeneity remains poorly understood. In this study, single cell RNA sequencing was conducted on multiple myeloma patients to investigate the role of FAM46C in tumor heterogeneity and extramedullary metastasis prediction.