Targeted methylation sequencing of plasma cell-free DNA for cancer detection and classification
Targeted methylation sequencing of plasma cell-free DNA for cancer detection and classification
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血浆游离DNA的靶向甲基化测序用于癌症检测和分类
DOI：
10.1093/annonc/mdy119
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发表时间：
2018-06-01
影响因子：
50.5
通讯作者：
Janku, F.
中科院分区：
文献类型：
--
作者：
Liu, L.;Toung, J. M.;Janku, F.
BackgroundTargeted methylation sequencing of plasma cell-free DNA（cfDNA）has a potential to expand liquid biopsies to patients with tumors without detectable oncogenic alterations，which can be potentially useful in early diagnosis.Patients and methodsWe developed a comprehensive methylation sequencing assay targeting 9223 CpG sites consistently hypermethylated according to The Cancer Genome Atlas.接下来，我们进行了我们的方法使用血浆cfDNA样本从78例晚期结直肠癌，非小细胞肺癌（NSCLC），乳腺癌或黑色素瘤的临床验证，并比较结果与患者outcome.ResultsMedian甲基化评分在血浆cfDNA样本从治疗的患者低于从患者关闭治疗（4.74与85.29; P = 0.001）。在68份来自停止治疗患者的血浆样本中，甲基化评分检测到57份（83.8%）存在癌症，其中45份（78.9%）基于甲基化的签名准确分类了潜在的癌症类型。甲基化评分在检测结直肠癌（96.3%），其次是乳腺癌（91.7%），黑色素瘤（81.8%）和NSCLC（61.1%）方面最准确，在分类结直肠癌（88.5%）中的潜在癌症类型方面最准确，其次是NSCLC（81.8%），乳腺癌（72.7%）和黑色素瘤（55.6%）。低甲基化评分与高甲基化评分相比，（10.4 vs 4.4个月，P < 0.001）和更长的治疗失败时间（2.8个月对1.6个月，P = 0.016）结论来自常见晚期癌症患者的血浆cfDNA中9223个CpG位点的全面靶向甲基化测序检测癌症的存在和潜在的癌症类型，其具有高的甲基化水平。精度血浆cfDNA中的甲基化评分与治疗结果相对应。
BackgroundTargeted methylation sequencing of plasma cell-free DNA (cfDNA) has a potential to expand liquid biopsies to patients with tumors without detectable oncogenic alterations, which can be potentially useful in early diagnosis.Patients and methodsWe developed a comprehensive methylation sequencing assay targeting 9223 CpG sites consistently hypermethylated according to The Cancer Genome Atlas. Next, we carried out a clinical validation of our method using plasma cfDNA samples from 78 patients with advanced colorectal cancer, non-small-cell lung cancer (NSCLC), breast cancer or melanoma and compared results with patients outcomes.ResultsMedian methylation scores in plasma cfDNA samples from patients on therapy were lower than from patients off therapy (4.74 versus 85.29; P = 0.001). Of 68 plasma samples from patients off therapy, methylation scores detected the presence of cancer in 57 (83.8%), and methylation-based signatures accurately classified the underlying cancer type in 45 (78.9%) of these. Methylation scores were most accurate in detecting colorectal cancer (96.3%), followed by breast cancer (91.7%), melanoma (81.8%) and NSCLC (61.1%), and most accurate in classifying the underlying cancer type in colorectal cancer (88.5%), followed by NSCLC (81.8%), breast cancer (72.7%) and melanoma (55.6%). Low methylation scores versus high were associated with longer survival (10.4 versus 4.4 months, P < 0.001) and longer time-to-treatment failure (2.8 versus 1.6 months, P = 0.016).ConclusionsComprehensive targeted methylation sequencing of 9223 CpG sites in plasma cfDNA from patients with common advanced cancers detects the presence of cancer and underlying cancer type with high accuracy. Methylation scores in plasma cfDNA correspond with treatment outcomes.