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PLoS Genet:循环肿瘤DNA片段更短小 有助开发液体活检新技术

2016-07-20 佚名 生物谷

DNA

根据一项发表在国际学术期刊Plos Genetics上的最新研究,循环肿瘤DNA与正常游离DNA在长度上存在差别,据此或可利用病人血液帮助开发检测肿瘤DNA的液体活检新技术。 液体活检技术可以从血液中发现和诊断癌症,还可以帮助监测癌症复发,评估治疗效果,但是这项技术仍然存在监测灵敏度的问题,大大限制了该技术的发展。美国犹他大学和华盛顿大学的研究人员发现,相比于正常细胞的DNA片段,来源于肿瘤细

根据一项发表在国际学术期刊Plos Genetics上的最新研究,循环肿瘤DNA与正常游离DNA在长度上存在差别,据此或可利用病人血液帮助开发检测肿瘤DNA的液体活检新技术。

液体活检技术可以从血液中发现和诊断癌症,还可以帮助监测癌症复发,评估治疗效果,但是这项技术仍然存在监测灵敏度的问题,大大限制了该技术的发展。美国犹他大学和华盛顿大学的研究人员发现,相比于正常细胞的DNA片段,来源于肿瘤细胞的循环DNA长度更短。

文章作者Hunter Underhill表示:“根据不同来源的循环DNA片段长度不同,可以检测到实体瘤的存在。”

研究人员在多形性成胶质细胞瘤小鼠模型中发现了上述现象。在研究中他们将人的多形性成胶质细胞瘤干细胞样系导入小鼠脑部,随后在血液中检测到了人类ctDNA,他们对比了人类肿瘤来源ctDNA和小鼠正常游离DNA的差别,发现人类ctDNA的长度一般为134个碱基,而小鼠正常游离DNA长度一般为167个碱基。研究人员还将人类肝细胞癌细胞植入小鼠体内也发现了类似现象,这表明循环肿瘤DNA长度更短是相对普遍的现象。

随后研究人员还对黑色素瘤患者和健康人体内的游离DNA进行了对比,他们发现黑色素瘤患者的游离DNA片段普遍更短。他们还对比了肺癌患者和健康人的游离DNA,结果表明肺癌患者来源的游离DNA长度也更短小。

研究人员对比了来自于EGFR T790M突变肺癌患者和健康人循环DNA测序文库,结果发现当DNA片段比平均长度短20到50个碱基时,该片段等位基因的突变率提升2.5到9.1倍。这说明短的游离DNA可提示更高的等位基因突变率。

作者表示,对短的游离DNA进行准确筛查将有助于等位基因突变及肿瘤的发现,但其中的机制还需要更多研究进行进一步揭示。

原始出处

Hunter R. Underhill ,Jacob O. Kitzman,Sabine Hellwig,Noah C. Welker,Riza Daza,Daniel N. Baker,Keith M. Gligorich,Robert C. Rostomily,Mary P. Bronner,Jay Shendure.Fragment Length of Circulating Tumor DNA.PLoS Genet.2016

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    2016-09-30 canlab
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    2016-07-21 cy0324
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    2016-07-22 smlt2008
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