Extracellular vesicles or free circulating DNA: where to search for BRAF and cKIT mutations?
Extracellular vesicles or free circulating DNA: where to search for BRAF and cKIT mutations?
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DOI：
10.1016/j.nano.2017.12.009
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发表时间：
2018-04-01
影响因子：
5.4
通讯作者：
Nazarenko, Irina
中科院分区：
文献类型：
--
作者：
Klump, Jennifer;Phillipp, Ulrike;Nazarenko, Irina
肿瘤学的临床证据表明，进行血液生物标志物的分子分析，以提供有关系统性变化和肿瘤异质性的信息的优势，而无细胞循环DNA（fcDNA）的诊断价值已成功地证明在几项研究中，封闭在细胞外囊泡（EV）的DNA最近才被描述，其潜在的诊断价值尚不清楚。我们建立了分离EV和fc组分的方案，并测试了黑色素瘤和肥大细胞增多症患者血液中介导对维罗非尼耐药性的突变体BRAFV600 E和介导对伊马替尼耐药性的cKITD816 V的存在。我们的研究结果表明，EV含有显着更高的量的总DNA相比，fc部分。然而，在fcDNA组分中检测到约10倍高拷贝数的野生型和突变型BRAF和cKIT，支持其诊断价值，并指出fc和EV DNA含量的差异。(c)2017爱思唯尔公司All rights reserved.
Clinical evidence in oncology argues for the advantages of performing molecular analysis of blood biomarkers to provide information about systemic changes and tumor heterogeneity.Whereas the diagnostic value of cell-free circulating DNA (fcDNA) has successfully been demonstrated in several studies, DNA enclosed in extracellular vesicles (EV) has only recently been described, and its potential diagnostic value is unclear. We established a protocol for separation of EV and fc fractions and tested for presence of mutant BRAFV600E mediating resistance to Vemurafenib and cKITD816V mediating resistance to Imatinib in blood of patients with melanoma and mastocytosis. Our results show that EV contain significantly higher amounts of total DNA as compared to the fc fraction. However, about ten-fold higher copy numbers of the wild type and mutant BRAF and cKIT were detected in the fcDNA fraction supporting its diagnostic value and pointing to differences in fc and EV DNA content. (c) 2017 Elsevier Inc. All rights reserved.