Genomic approaches to cancer and minimal residual disease detection using circulating tumor DNA.
Genomic approaches to cancer and minimal residual disease detection using circulating tumor DNA.
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DOI：
10.1136/jitc-2022-006284
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发表时间：
2023-06
影响因子：
10.9
通讯作者：
中科院分区：
文献类型：
--
作者：
使用无细胞循环肿瘤 DNA (ctDNA) 的液体活检在研究和临床环境中经常使用。 ctDNA 可用于识别可操作的突变，以实现个性化全身治疗、检测治疗后微小残留病 (MRD) 并预测对免疫治疗的反应。 ctDNA 还可以从一系列不同的生物体液中分离出来，如果采样距离比血浆更近，则可以提高检测局部 MRD 的灵敏度。然而，ctDNA 检测在早期和治疗后 MRD 环境中仍然具有挑战性，其中 ctDNA 水平极低，假阴性结果的风险很高，这与克隆造血的假阳性结果的风险相平衡。为了应对这些挑战，研究人员开发了更加优雅的方法，通过减少低水平的技术和生物噪音来源以及利用 ctDNA 的特定基因组和表观基因组特征，将 ctDNA 检测的检测限 (LOD) 降低到百万分之一范围，并提高检测灵敏度和特异性。在这篇综述中，我们重点介绍了一系列用于 ctDNA 分析的现代检测方法，包括在提高信噪比方面取得的进展。我们进一步强调了检测极其罕见的肿瘤相关变异的挑战，克服这一挑战将提高治疗后 MRD 检测的灵敏度，并开辟个性化辅助治疗决策的新领域。
Liquid biopsies using cell-free circulating tumor DNA (ctDNA) are being used frequently in both research and clinical settings. ctDNA can be used to identify actionable mutations to personalize systemic therapy, detect post-treatment minimal residual disease (MRD), and predict responses to immunotherapy. ctDNA can also be isolated from a range of different biofluids, with the possibility of detecting locoregional MRD with increased sensitivity if sampling more proximally than blood plasma. However, ctDNA detection remains challenging in early-stage and post-treatment MRD settings where ctDNA levels are minuscule giving a high risk for false negative results, which is balanced with the risk of false positive results from clonal hematopoiesis. To address these challenges, researchers have developed ever-more elegant approaches to lower the limit of detection (LOD) of ctDNA assays toward the part-per-million range and boost assay sensitivity and specificity by reducing sources of low-level technical and biological noise, and by harnessing specific genomic and epigenomic features of ctDNA. In this review, we highlight a range of modern assays for ctDNA analysis, including advancements made to improve the signal-to-noise ratio. We further highlight the challenge of detecting ultra-rare tumor-associated variants, overcoming which will improve the sensitivity of post-treatment MRD detection and open a new frontier of personalized adjuvant treatment decision-making.
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影响因子：
16.6
作者：
An, Yunyun;Zhao, Xin;Zhang, Ziteng;Xia, Zhaohua;Yang, Mengqi;Ma, Li;Zhao, Yu;Xu, Gang;Du, Shunda;Wu, Xiang'an;Zhang, Shuowen;Hong, Xin;Jin, Xin;Sun, Kun
通讯作者：
Sun, Kun
宇宙（癌症中的体细胞突变目录）数据库和网站。
影响因子：
8.8
作者：
Bamford, S;Dawson, E;Forbes, S;Clements, J;Pettett, R;Dogan, A;Flanagan, A;Teague, J;Futreal, PA;Stratton, MR;Wooster, R
通讯作者：
Wooster, R
影响因子：
13.6
作者：
Avanzini S;Kurtz DM;Chabon JJ;Moding EJ;Hori SS;Gambhir SS;Alizadeh AA;Diehn M;Reiter JG
通讯作者：
Reiter JG
影响因子：
46.9
作者：
Cohen JD;Douville C;Dudley JC;Mog BJ;Popoli M;Ptak J;Dobbyn L;Silliman N;Schaefer J;Tie J;Gibbs P;Tomasetti C;Papadopoulos N;Kinzler KW;Vogelstein B
通讯作者：
Vogelstein B
影响因子：
15.8
作者：
Chauhan PS;Chen K;Babbra RK;Feng W;Pejovic N;Nallicheri A;Harris PK;Dienstbach K;Atkocius A;Maguire L;Qaium F;Szymanski JJ;Baumann BC;Ding L;Cao D;Reimers MA;Kim EH;Smith ZL;Arora VK;Chaudhuri AA
通讯作者：
Chaudhuri AA