Nature Commun:转移性癌症患者有望从液体活检中受益

2017-11-07 佚名 生物通

通过检测血液中的游离DNA(cfDNA),究竟能否提供癌症的线索,这个问题困扰了人们很久。近日,Broad研究所的研究人员在《Nature Communications》上发表文章称,90%的肿瘤遗传特征可通过血液样本的全外显子组测序检测到,这种方法可应用在近半的晚期癌症患者身上。


通过检测血液中的游离DNA(cfDNA),究竟能否提供癌症的线索,这个问题困扰了人们很久。近日,Broad研究所的研究人员在《Nature Communications》上发表文章称,90%的肿瘤遗传特征可通过血液样本的全外显子组测序检测到,这种方法可应用在近半的晚期癌症患者身上。

通讯作者之一、Broad研究所的Viktor Adalsteinsson博士表示:“我们的最终目标是利用血液活检来全面搜索和鉴定哪怕是最小的肿瘤残留。随着肿瘤进展到晚期,形成耐药性或成为转移瘤,我们希望在关键的时间点介入,决定哪种疗法最适合患者。”

对癌症患者而言,侵入性的手术活检是痛苦且困难的,而且有些肿瘤的位置很难触及。如今,液体活检正成为一种新兴的替代方法。通过检测和分析患者血液样本中的癌症DNA,它有望克服传统活检的问题,让医生可实时追踪疾病进展和治疗情况,并帮助研究人员了解肿瘤的耐药性如何形成。

收集DNA片段的全外显子组,需要血液样本中至少有10%的肿瘤DNA,但这个比例因患者而异。基于此,研究人员首先需要一种无偏倚的方法来测定癌症DNA的水平,然后再开展测序。目前的许多血液活检方法是筛查已知的癌症相关基因,但这种靶向重测序方法可能会漏掉一些癌症。

在这项研究中,研究人员开发出一种称为ichorCNA的工具,它能够分析癌症基因组中普遍存在的各种突变模式,捕获带有已知和未知突变的癌症。此外,他们重点检测了癌细胞中拷贝数过高或过低的DNA片段。总共有1439个血液样本被检测,它们来自520名转移性乳腺癌或前列腺癌患者。

利用这种方法,研究人员发现在33%到49%的转移性癌症患者中,肿瘤DNA的含量超过了游离DNA的10%。这意味着游离DNA的全外显子组测序是可行的。“我们的研究已经证明,我们能够从血液中可靠地获得癌症外显子组。它与肿瘤活检相匹配,对相当一部分转移性癌症患者有用,”Adalsteinsson博士指出。

之后,研究人员对41名患者开展进一步分析,将肿瘤活检结果与游离DNA的外显子测序数据相比较。他们发现,外显子组测序和组织活检的遗传数据在很大程度上匹配,比如体细胞突变的匹配度达88%,拷贝数改变的匹配度达80%。这些结果表明,游离DNA的全外显子组测序有望替代许多患者的转移性肿瘤活检。

总的来说,这项新的研究改进了血液活检的分析流程,使其能够在更大范围内开展。研究人员正在积极地将这项成果应用在数千名转移性癌症患者上。“这项技术让我们能够追踪癌症的动态变化,了解耐药性的演化以及转移性状态的发展,这是手术活检无法实现的,”Broad研究所的Gad Getz谈道。

原始出处:

Viktor A. Adalsteinsson, Gavin Ha, Samuel S,et al. Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors.Nature Communications 8, Article number: 1324 (2017) doi:10.1038/s41467-017-00965-y

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    2018-02-05 一叶知秋
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    2017-12-04 liuli5079
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    2017-11-09 smlt2008
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    2017-11-09 yfjms

    学习

    0

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    2017-11-07 有备才能无患

    如今.液体活检正成为一种新兴的替代方法.通过检测和分析患者血液样本中的癌症DNA.它有望克服传统活检的问题.让医生可实时追踪疾病进展和治疗情况.并帮助研究人员了解肿瘤的耐药性如何形成.

    0

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    2017-11-07 清风拂面

    学习了.很好的文章

    0

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