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通过识别DNA差异快速进行癌症初步诊断|NCOMMS论文 |
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论文标题：Epigenetically reprogrammed methylation landscape drives the DNA self-assembly and serves as a universal cancer biomarker
期刊：
作者：Abu Ali Ibn Sina, Laura G. Carrascosa, Ziyu Liang, Yadveer S. Grewal, Andri Wardiana, Muhammad J. A. Shiddiky, Robert A. Gardiner, Hemamali Samaratunga, Maher K. Gandhi, Rodney J. Scott, Darren Korbie, Matt Trau
发表时间：2018/11/04
原文链接：
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《自然-通讯》本周发表的一篇论文Epigenetically reprogrammed methylation landscape drives the DNA self-assembly and serves as a universal cancer biomarker手机版了一项能在10分钟内完成的癌细胞检测。这项检测通过识别癌细胞和健康细胞之间的DNA差异，快速完成初步诊断。
图1：表观遗传重编程调节基因组DNA的物理明升手机特性。图源：Sina等
甲基基团附着到DNA上的过程（这一过程被称为甲基化）受到遗传操控。在所有“成熟”的人类细胞中，DNA都携带这些修饰。癌细胞与健康细胞的基因组信息具有显著差异，进而导致大多数类型的癌细胞中甲基化水平和模式的差异。
澳大利亚昆士兰大学的Matt Trau及同事发现，癌细胞中不同的甲基化情况会影响DNA的物理和明升手机性质。在这些特性中，作者发现DNA与金纳米粒子的连接尤为紧密，并利用这一特性开发出了一种癌症检测方法。只需极少量来自患者的纯化的基因组DNA，就能在10分钟内完成检测，且检测结果仅靠肉眼就能辨别。作者在代表了不同癌症类型的100多个人类样本（72名癌症患者和31名健康个体的基因组DNA）中测试了这一方法。
图2：甲基化对DNA-金亲疏性的作用。图源： Sina等
在目前的阶段，此方法只能检测是否有癌细胞存在，但无法识别其类型或疾病进展。今后应对更多样本进行测试，并在可能的情况下开展更详细的分析研究。
摘要：Epigenetic reprogramming in cancer genomes creates a distinct methylation landscape encompassing clustered methylation at regulatory regions separated by large intergenic tracks of hypomethylated regions. This methylation landscape that we referred to as Methylscape is displayed by most cancer types, thus may serve as a universal cancer biomarker. To-date most research has focused on the biological consequences of DNA Methylscape changes whereas its impact on DNA physicochemical properties remains unexplored. Herein, we examine the effect of levels and genomic distribution of methylcytosines on the physicochemical properties of DNA to detect the Methylscape biomarker. We find that DNA polymeric behaviour is strongly affected by differential patterning of methylcytosine, leading to fundamental differences in DNA solvation and DNA-gold affinity between cancerous and normal genomes. We exploit these Methylscape differences to develop simple, highly sensitive and selective electrochemical or colorimetric one-step assays for the detection of cancer. These assays are quick, i.e., analysis time ≤10 minutes, and require minimal sample preparation and small DNA input.
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