Østrup Olga, Ahlborn Lise Barlebo, Lassen Ulrik, Mau-Sørensen Morten, Nielsen Finn Cilius
Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
Department of Oncology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
BBA Clin. 2017 Apr 4;7:120-126. doi: 10.1016/j.bbacli.2017.03.006. eCollection 2017 Jun.
Somatic copy number alterations (SCNAs) occurring in tumors can provide information about tumor classification, patient's outcome or treatment targets. Liquid biopsies, incl. plasma samples containing circulating cell-free tumor DNA (ccfDNA) can be used to assess SCNAs for clinical purposes, however specify and reliability of methods have to be tested.
SNP microarrays (Affymetrix) were used to generate whole-genome copy number profiles from plasma ccfDNA (OncoScan) and paired tumor biopsies (CytoScan) from ten patients with metastatic cancers. Numerical, segmental and focal SCNAs were assessed using ASCAT/TuScan and SNP-FASST2.
Aberrations in ccfDNA in 4 patients resembled numerical (76%) and segmental (80%) aberrations in tDNA. Three patients represented low correlation due to postponed sampling time, ccfDNA quality and possible treatment interference. Breakpoints of high-amplitude amplification were assessed with high accuracy and relative breakpoints difference of only 7% (0.02-37%). Similarly, biallelic losses were reliably detected. Array was 100% successful in detection of SCNAs on clinically relevant genes compared to SCNAs in tumor biopsies. Tracking of SCNAs changes during the treatment course of one patient also indicated that apoptosis/necrosis of non-cancerous cells presumably induced by treatment can influence ccfDNA composition and introduce false-negative findings into the analysis of liquid biopsies.
Genomic alterations detected in ccfDNA from liquid biopsies by comprehensive SNP array are reliable source for information for stratification of patients for targeted treatment.
Clinically relevant SCNAs can be detected in ccfDNA with high resolution and can therefore serve as an alternative to tumor biopsy in defining treatment targets.
肿瘤中发生的体细胞拷贝数改变（SCNAs）可为肿瘤分类、患者预后或治疗靶点提供信息。液体活检，包括含有循环游离肿瘤DNA（ccfDNA）的血浆样本，可用于评估SCNAs以用于临床目的，然而方法的特异性和可靠性必须进行测试。
使用SNP微阵列（Affymetrix）从10例转移性癌症患者的血浆ccfDNA（OncoScan）和配对的肿瘤活检样本（CytoScan）中生成全基因组拷贝数图谱。使用ASCAT/TuScan和SNP-FASST2评估数值性、节段性和局灶性SCNAs。
4例患者的ccfDNA中的畸变与肿瘤DNA中的数值性（76%）和节段性（80%）畸变相似。3例患者由于采样时间延迟、ccfDNA质量和可能的治疗干扰而呈现低相关性。高振幅扩增的断点评估具有高精度，相对断点差异仅为7%（0.02 - 37%）。同样，双等位基因缺失也能被可靠检测到。与肿瘤活检中的SCNAs相比，该阵列在检测临床相关基因上的SCNAs时成功率为100%。对1例患者治疗过程中SCNAs变化的追踪还表明，治疗可能诱导的非癌细胞凋亡/坏死会影响ccfDNA组成，并在液体活检分析中引入假阴性结果。
通过综合SNP阵列在液体活检的ccfDNA中检测到的基因组改变是用于患者分层以进行靶向治疗的可靠信息来源。
可在ccfDNA中以高分辨率检测到临床相关的SCNAs，因此在确定治疗靶点方面可作为肿瘤活检的替代方法。
