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• W2808793209 abstract "Abstract Background: We previously reported that circulating tumor cells (CTCs) from myeloma patients and clonal plasma cells from the BM biopsy of the same patients have quite similar clonal structures (Cell Rep. 2017;19(1):218). Specifically, overall, 90% of CTC mutations were present in BM tumors and 93% of BM mutations were present in CTC samples, and upon analyzing the mutational variants by nucleotide change, we found that the percentages of each change in BM myeloma PCs and CTCs were concordant. This finding suggests the possibility that multiple lesions of a multiple myeloma patient basically share similar clonal structure. Methods: To examine this hypothesis, we performed xenograft dissemination model of multiple myeloma using DNA-barcoded cell library. Briefly, two million human multiple myeloma cell lines barcoded with 12mer-DNA tags were inoculated into the bone chips harvested from syngeneic donor mice and the tumor-bearing bone chips were implanted to recipient mice. After the implanted myeloma cells were disseminated to murine host bone marrow via hematogenous dissemination, tumor cells were harvested from multiple BM sites and peripheral blood then analyzed the clonal structure by next-generation sequencing. Results: The clonal structures of tumor cells were highly concordant between left and right femur bone marrow from same mice. In addition, the clonal structures of tumor in host murine bone marrow were also highly concordant with those of CTCs harvested from same mice as we observed in clinical samples previously. Discussion: Recent studies of massive parallel sequencing of tumor cells obtained from the BM of patients with MM have demonstrated significant intrapatient clonal heterogeneity. Most patients have both clonal and subclonal variants even in single biopsy site. In a previous study, we have shown that the variant landscapes of tumors were highly concordant between CTCs and single BM biopsy specimen in same patients. Together with these findings, the result of our xenograft model may indicate that the tumor lesions of myeloma patients basically consist of heterogeneous but highly shared tumor cell population across the multiple lesions. The concordance of clonal structures among the multiple BM lesions is thought to be due to the fact that the clonal structure of BM myeloma tumors reflects that of CTC. Together, this study supports validity of the CTC for genetic profiling. Citation Format: Yuji Mishima, Yasuhito Terui, Kiyohiko Hatake. Intrapatient heterogeneity of multiple myeloma is evenly distributed in multiple myeloma lesions [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A015." @default.
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• W2808793209 date "2018-01-01" @default.
• W2808793209 modified "2023-09-27" @default.
• W2808793209 title "Abstract A015: Intrapatient heterogeneity of multiple myeloma is evenly distributed in multiple myeloma lesions" @default.
• W2808793209 doi "https://doi.org/10.1158/1535-7163.targ-17-a015" @default.
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