The Mutational Landscape of Circulating Tumor Cells in Multiple Myeloma.
The Mutational Landscape of Circulating Tumor Cells in Multiple Myeloma.
复制标题
DOI：
10.1016/j.celrep.2017.03.025
复制
发表时间：
2017-04-04
期刊：
影响因子：
8.8
通讯作者：
Ghobrial IM
中科院分区：
文献类型：
--
作者：
Mishima Y;Paiva B;Shi J;Park J;Manier S;Takagi S;Massoud M;Perilla-Glen A;Aljawai Y;Huynh D;Roccaro AM;Sacco A;Capelletti M;Detappe A;Alignani D;Anderson KC;Munshi NC;Prosper F;Lohr JG;Ha G;Freeman SS;Van Allen EM;Adalsteinsson VA;Michor F;San Miguel JF;Ghobrial IM
灵敏和非侵入性的“液体活检”的发展为肿瘤扩散和克隆进化的纵向监测提供了新的机会。循环肿瘤细胞（CTC）的数量是多发性骨髓瘤（MM）的预后指标，但关于其遗传特征的信息很少。在这里，我们分析了来自29名MM患者的CTC的基因组景观，其中包括8例匹配/配对的骨髓（BM）肿瘤细胞。我们的研究结果表明，患者BM中100%的克隆突变在CTC中检测到，CTC中99%的克隆突变存在于BM MM中。这些包括MM中的典型驱动突变，如KRAS、NRAS或BRAF。这些数据表明，BM和CTC样品具有相似的克隆结构，因为两者之间的不一致仅限于亚克隆突变。因此，我们的研究结果为通过CTC的表征对MM患者进行潜在的侵入性较小的突变筛查铺平了道路。
The development of sensitive and non-invasive “liquid biopsies” presents new opportunities for longitudinal monitoring of tumor dissemination and clonal evolution. The number of circulating tumor cells (CTCs) is prognostic in multiple myeloma (MM), but there is little information on their genetic features. Here, we have analyzed the genomic landscape of CTCs from 29 MM patients, including eight cases with matched/paired bone marrow (BM) tumor cells. Our results show that 100% of clonal mutations in patient BM were detected in CTCs and that 99% of clonal mutations in CTCs were present in BM MM. These include typical driver mutations in MM such as in KRAS, NRAS, or BRAF. These data suggest that BM and CTC samples have similar clonal structures, as discordances between the two were restricted to subclonal mutations. Accordingly, our results pave the way for potentially less invasive mutation screening of MM patients through characterization of CTCs.