Individualised multiplexed circulating tumour DNA assays for monitoring of tumour presence in patients after colorectal cancer surgery.
Individualised multiplexed circulating tumour DNA assays for monitoring of tumour presence in patients after colorectal cancer surgery.
复制标题
个体化多重循环肿瘤 DNA 检测，用于监测结直肠癌手术后患者肿瘤的存在。
DOI：
10.1038/srep40737
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发表时间：
2017-01-19
影响因子：
4.6
通讯作者：
Tan IB
中科院分区：
文献类型：
--
作者：
Ng SB;Chua C;Ng M;Gan A;Poon PS;Teo M;Fu C;Leow WQ;Lim KH;Chung A;Koo SL;Choo SP;Ho D;Rozen S;Tan P;Wong M;Burkholder WF;Tan IB
循环肿瘤DNA（ctDNA）有可能成为监测结直肠癌（CRC）患者肿瘤的特异性生物标志物。在这里，我们的目标是制定一个个性化的监测策略，以监测手术后CRC的临床过程。我们基于从患者原发性肿瘤中鉴定的体细胞突变的多重检测开发了患者特异性ctDNA测定，并将其应用于检测44名CRC患者的ctDNA，分析了总共260份血浆样本。我们发现ctDNA检测与临床事件相关-它在术前但术后血浆中可检测到，并且在复发性CRC患者中也可检测到。我们还在15例CRC临床或放射学复发时或之前的11例中检测到ctDNA，表明我们的检测方法用于早期检测转移的潜力。我们进一步提供了来自患有多种原发性癌症的患者的数据，以证明我们的检测方法在区分CRC复发和第二原发性癌症方面的特异性。我们的方法可以通过添加个性化的生物成分来补充目前的CRC监测方法，使我们不仅能够指出残留或复发疾病的存在，而且还可以将其归因于原始癌症。
Circulating tumour DNA (ctDNA) has the potential to be a specific biomarker for the monitoring of tumours in patients with colorectal cancer (CRC). Here, our aim was to develop a personalised surveillance strategy to monitor the clinical course of CRC after surgery. We developed patient-specific ctDNA assays based on multiplexed detection of somatic mutations identified from patient primary tumours, and applied them to detect ctDNA in 44 CRC patients, analysing a total of 260 plasma samples. We found that ctDNA detection correlated with clinical events – it is detectable in pre-operative but not post-operative plasma, and also in patients with recurrent CRC. We also detected ctDNA in 11 out of 15 cases at or before clinical or radiological recurrence of CRC, indicating the potential of our assay for early detection of metastasis. We further present data from a patient with multiple primary cancers to demonstrate the specificity of our assays to distinguish between CRC recurrence and a second primary cancer. Our approach can complement current methods for surveillance of CRC by adding an individualised biological component, allowing us not only to point to the presence of residual or recurrent disease, but also attribute it to the original cancer.