Li Qian, Huang Helen J, Ma Jing, Wang Yafei, Cao Zeng, Karlin-Neumann George, Janku Filip, Liu Zhiqiang
Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Tianjin Key Laboratory of Cancer Prevention and Therapy; Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
J Cancer. 2020 Mar 15;11(12):3543-3550. doi: 10.7150/jca.43729. eCollection 2020.
: To evaluate the detection of gene mutations in bone marrow biopsy and circulating free DNA (cfDNA) from plasma in multiple myeloma (MM). : We used cell-free DNA from plasma and bone marrow to test , , and mutations using multiplex assays for droplet digital PCR (ddPCR), and evaluated results with clinical outcomes. : We found of 83 patients, the detectable mutation frequencies for the above four genes were 4 (5%), 13 (16%), 3 (4%) and 14 (17%) in bone marrow, respectively. The median variant allelic frequency (VAF) in most mutations were 1.595%. In 17 paired cfDNA samples, the detectable mutation frequencies for the above four genes were 5 (30%), 1 (6%), 0 (0%) and 3 (18%) respectively, and the median VAF rate was 2.9%. Agreement between bone marrow DNA and plasma cfDNA were 76%, 100%, 100% and 100% compared to the tissue detections, respectively. In 17 patients with paired bone marrow and plasma samples, the above four mutations were 3 (18%), 1 (6%), 0 (0%) and 2 (12%) respectively, with the agreement rates of 88%, 88%, 100% and 100% compared to tissue detections. Of 57 patients with available outcome data, high mutation VAF had a shorter median survival than patients with low mutation VAF (=0.0322). : Oncogenic mutations in , and genes can be detected in the bone marrow and plasma cfDNA with ddPCR in patients with MM patients and high VAF is associated with short survival.
评估多发性骨髓瘤（MM）患者骨髓活检及血浆循环游离DNA（cfDNA）中基因突变的检测情况。我们使用血浆和骨髓中的游离DNA，通过液滴数字PCR（ddPCR）多重检测法检测 、 、 和 基因突变，并将结果与临床结局进行评估。我们发现，83例患者中，上述四个基因在骨髓中的可检测突变频率分别为4例（5%）、13例（16%）、3例（4%）和14例（17%）。大多数突变的中位变异等位基因频率（VAF）为1.595%。在17对cfDNA样本中，上述四个基因的可检测突变频率分别为5例（30%）、1例（6%）、0例（0%）和3例（18%），中位VAF率为2.9%。与组织检测相比，骨髓DNA与血浆cfDNA的一致性分别为76%、100%、100%和100%。在17例有配对骨髓和血浆样本的患者中，上述四种突变分别为3例（18%）、1例（6%）、0例（0%）和2例（12%），与组织检测的一致率分别为88%、88%、100%和100%。在57例有可用结局数据的患者中，高突变VAF患者的中位生存期比低突变VAF患者短（ =0.0322）。在MM患者中，可通过ddPCR在骨髓和血浆cfDNA中检测到 、 和 基因的致癌突变，高VAF与生存期短相关。
