Cancer Genome Scanning in Plasma: Detection of Tumor-Associated Copy Number Aberrations, Single-Nucleotide Variants, and Tumoral Heterogeneity by Massively Parallel Sequencing
Cancer Genome Scanning in Plasma: Detection of Tumor-Associated Copy Number Aberrations, Single-Nucleotide Variants, and Tumoral Heterogeneity by Massively Parallel Sequencing
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DOI：
10.1373/clinchem.2012.196014
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发表时间：
2013-01-01
影响因子：
9.3
通讯作者：
Lo, Y. M. D.
中科院分区：
文献类型：
--
作者：
Chan, K. C. Allen;Jiang, Peiyong;Lo, Y. M. D.
背景：肿瘤来源的DNA可以在癌症患者的血浆中发现。在这项研究中，我们探索了使用霰弹枪大规模平行测序（MPS）从癌症患者的血浆DNA扫描癌症基因组无创。方法：招募4例肝细胞癌患者和1例同步乳腺癌和卵巢癌患者。从肿瘤组织中提取DNA，并对患者术前和术后血浆样本进行霰弹枪MPS分析。结果：我们获得了肿瘤患者血浆中拷贝数畸变和点突变的全基因组图谱。通过检测和量化全基因组聚集的等位基因丢失和点突变，我们确定了血浆中肿瘤来源DNA的分数浓度，并将这些值与肿瘤大小和手术治疗相关联。我们还通过研究患有两种同步癌症的患者，证明了这种方法在复杂肿瘤情况分析中的潜在效用。通过使用肿瘤组织的多区域测序和血浆DNA的散弹枪测序，我们已经证明血浆DNA测序是研究肿瘤异质性的一种有价值的方法。结论：血浆散弹枪DNA测序是癌症检测、监测和研究的潜在有力工具。(C) 2012美国临床化学学会
BACKGROUND: Tumor-derived DNA can be found in the plasma of cancer patients. In this study, we explored the use of shotgun massively parallel sequencing (MPS) of plasma DNA from cancer patients to scan a cancer genome noninvasively.METHODS: Four hepatocellular carcinoma patients and a patient with synchronous breast and ovarian cancers were recruited. DNA was extracted from the tumor tissues, and the preoperative and postoperative plasma samples of these patients were analyzed with shotgun MPS.RESULTS: We achieved the genomewide profiling of copy number aberrations and point mutations in the plasma of the cancer patients. By detecting and quantifying the genomewide aggregated allelic loss and point mutations, we determined the fractional concentrations of tumor-derived DNA in plasma and correlated these values with tumor size and surgical treatment. We also demonstrated the potential utility of this approach for the analysis of complex oncologic scenarios by studying the patient with 2 synchronous cancers. Through the use of multiregional sequencing of tumoral tissues and shotgun sequencing of plasma DNA, we have shown that plasma DNA sequencing is a valuable approach for studying tumoral heterogeneity.CONCLUSIONS: Shotgun DNA sequencing of plasma is a potentially powerful tool for cancer detection, monitoring, and research. (C) 2012 American Association for Clinical Chemistry