小儿肿瘤中ctDNA的研究进展

doi:10.3969/j.issn.1004-583X.2025.08.017

摘要/Abstract

摘要：

小儿恶性肿瘤是现如今导致儿童死亡的主要疾病之一,虽然各种治疗手段不断进步,但部分恶性肿瘤的复发和耐药,仍是预后不良的关键因素。循环肿瘤DNA(circulating tumor DNA,ctDNA),为检测血浆中癌症特异性标志物的一种微创工具,越来越受到重视,在成人癌症中,ctDNA检测已显示出在疾病监测应用中的价值,包括肿瘤突变谱分析、风险分层、复发预测和治疗反应评估。目前,ctDNA已在成人多种肿瘤的诊断和治疗效果预测中进行使用且越来越被临床所接受,但在儿童肿瘤的使用目前仍具有一定局限性。本文系统综述ctDNA在小儿肿瘤中的生物学特性、检测技术、临床应用现状及挑战,并结合最新研究探讨其未来发展方向,为推动精准医疗在儿科肿瘤中的应用提供理论依据。

关键词: 肿瘤, 循环肿瘤DNA, 微小残留病灶, 液体活检, 精准医疗

中图分类号:

R739.9

滕怀千, 萧俊, 肖龙敏, 王安琪. 小儿肿瘤中ctDNA的研究进展[J]. 临床荟萃, 2025, 40(8): 764-768.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://www.lchc.cn/CN/10.3969/j.issn.1004-583X.2025.08.017

https://www.lchc.cn/CN/Y2025/V40/I8/764

参考文献 48

[1]	Lupo PJ, Spector LG. Cancer progress and priorities: Childhood cancer[J]. Cancer Epidemiol Biomarkers Prev, 2020, 29(6): 1081-1094.
[2]	Zahnreich S, Schmidberger H. Childhood cancer: Occurrence, treatment and risk of second primary malignancies[J]. Cancers (Basel), 2021, 13(11):2607.
[3]	Keller KM, Koetsier J, Schild L, et al. The potential of PARP as a therapeutic target across pediatric solid malignancies[J]. BMC Cancer, 2023, 23(1): 310. doi: 10.1186/s12885-022-10319-7 pmid: 37020198
[4]	Liu LP, Zong SY, Zhang AL, et al. Early detection of molecular residual disease and risk stratification for children with acute myeloid leukemia via circulating tumor DNA[J]. Clin Cancer Res, 2024, 30(6): 1143-1151. doi: 10.1158/1078-0432.CCR-23-2589 pmid: 38170574
[5]	Yeh JM, Ward ZJ, Chaudhry A, et al. Life expectancy of adult survivors of childhood cancer over 3 decades[J]. JAMA Oncol, 2020, 6(3): 350-357. doi: 10.1001/jamaoncol.2019.5582 pmid: 31895405
[6]	Peterson K, Turos-Cabal M, Salvador AD, et al. Mechanistic insights into medulloblastoma relapse[J]. Pharmacol Ther, 2024, 260: 108673.
[7]	Othman J, Potter N, Ivey A, et al. Postinduction molecular MRD identifies patients with NPM1 AML who benefit from allogeneic transplant in first remission[J]. Blood, 2024, 143(19): 1931-1936.
[8]	Herbst RS, John T, Grohé C, et al. Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB-IIIA non-small-cell lung cancer[J]. Nat Med, 2025, 31(6): 1958-1968.
[9]	Doculara L, Trahair TN, Bayat N, et al. Circulating tumor DNA in pediatric cancer[J]. Front Mol Biosci, 2022, 9: 885597.
[10]	Lei S, Jia S, Takalkar S, et al. Genomic profiling of circulating tumor DNA for childhood cancers[J]. Leukemia, 2025, 39(2): 420-430. doi: 10.1038/s41375-024-02461-x pmid: 39523434
[11]	Xu L, Kim ME, Polski A, et al. Establishing the clinical utility of ctDNA analysis for diagnosis, prognosis, and treatment monitoring of retinoblastoma: The aqueous humor liquid biopsy[J]. Cancers (Basel), 2021, 13(6):1282.
[12]	Kahana-Edwin S, Cain LE, Karpelowsky J. Roadmap to liquid biopsy biobanking from pediatric cancers-challenges and opportunities[J]. Biopreserv Biobank, 2021, 19(2): 124-129. doi: 10.1089/bio.2020.0117 pmid: 33493007
[13]	Vellanki PJ, Ghosh S, Pathak A, et al. Regulatory implications of ctDNA in immuno-oncology for solid tumors[J]. J Immunother Cancer, 2023, 11(2):e005344.
[14]	Ni X, Li Z, Li X, et al. Socioeconomic inequalities in cancer incidence and access to health services among children and adolescents in China: A cross-sectional study[J]. Lancet, 2022, 400(10357): 1020-1032. doi: 10.1016/S0140-6736(22)01541-0 pmid: 36154677
[15]	Garcia-Murillas I, Cutts RJ, Walsh-Crestani G, et al. Longitudinal monitoring of circulating tumor DNA to detect relapse early and predict outcome in early breast cancer[J]. Breast Cancer Res Treat, 2025, 209(3): 493-502.
[16]	Fan H, Wang B, Shi L, et al. Monitoring minimal residual disease in patients with multiple myeloma by targeted tracking serum m-protein using mass spectrometry (EasyM)[J]. Clin Cancer Res, 2024, 30(6): 1131-1142. doi: 10.1158/1078-0432.CCR-23-2767 pmid: 38170583
[17]	Diehl F, Schmidt K, Choti MA, et al. Circulating mutant DNA to assess tumor dynamics[J]. Nat Med, 2008, 14(9): 985-990. doi: 10.1038/nm.1789 pmid: 18670422
[18]	De Mattos-Arruda L, Mayor R, Ng CKY, et al. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma[J]. Nat Commun, 2015, 6: 8839. doi: 10.1038/ncomms9839 pmid: 26554728
[19]	Bosse KR, Giudice AM, Lane MV, et al. Serial profiling of circulating tumor DNA identifies dynamic evolution of clinically actionable genomic alterations in high-risk neuroblastoma[J]. Cancer Discov, 2022, 12(12): 2800-2819. doi: 10.1158/2159-8290.CD-22-0287 pmid: 36108156
[20]	Patel J, Aittaleb R, Doherty R, et al. Liquid biopsy in H3K27M diffuse midline glioma[J]. Neuro Oncol, 2024, 26(Supplement_2): S101-s109.
[21]	Combaret V, Hogarty MD, London WB, et al. Influence of neuroblastoma stage on serum-based detection of MYCN amplification[J]. Pediatr Blood Cancer, 2009, 53(3): 329-331. doi: 10.1002/pbc.22009 pmid: 19301388
[22]	Pagès M, Rotem D, Gydush G, et al. Liquid biopsy detection of genomic alterations in pediatric brain tumors from cell-free DNA in peripheral blood, CSF, and urine[J]. Neuro Oncol, 2022, 24(8): 1352-1363.
[23]	Pierce E, Mautner B, Mort J, et al. MRD in aLL: Optimization and innovations[J]. Curr Hematol Malig Rep, 2022, 17(4): 69-81.
[24]	Bellassai N, D'Agata R, Marti A, et al. Detection of tumor DNA in human plasma with a functional pll-based surface layer and plasmonic biosensing[J]. ACS Sens, 2021, 6(6): 2307-2319.
[25]	Escudero L, Llort A, Arias A, et al. Circulating tumour DNA from the cerebrospinal fluid allows the characterisation and monitoring of medulloblastoma[J]. Nat Commun, 2020, 11(1): 5376. doi: 10.1038/s41467-020-19175-0 pmid: 33110059
[26]	Newman AM, Bratman SV, To J, et al. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage[J]. Nat Med, 2014, 20(5): 548-554. doi: 10.1038/nm.3519 pmid: 24705333
[27]	Bettegowda C, Sausen M, Leary RJ, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies[J]. Sci Transl Med, 2014, 6(224): 224ra24.
[28]	Liu APY, Smith KS, Kumar R, et al. Serial assessment of measurable residual disease in medulloblastoma liquid biopsies[J]. Cancer Cell, 2021, 39(11): 1519-1530.e4. doi: 10.1016/j.ccell.2021.09.012 pmid: 34678152
[29]	Nelson AJ, Park S, Nelson MD Jr, et al. Aqueous humor liquid biopsy to exclude retinoblastoma for a child with an intraocular mass[J]. Case Rep Ophthalmol, 2025, 16(1): 366-371.
[30]	Conway AM, Pearce SP, Clipson A, et al. A cfDNA methylation-based tissue-of-origin classifier for cancers of unknown primary[J]. Nat Commun, 2024, 15(1): 3292.
[31]	Wu Y, Tilley RD, Gooding JJ. Challenges and solutions in developing ultrasensitive biosensors[J]. J Am Chem Soc, 2019, 141(3): 1162-1170. doi: 10.1021/jacs.8b09397 pmid: 30463401
[32]	Kahana-Edwin S, Cain LE, McCowage G, et al. Neuroblastoma molecular risk-stratification of DNA copy number and ALK genotyping via cell-free circulating tumor DNA profiling[J]. Cancers (Basel), 2021, 13(13):3365.
[33]	Nirgude S, Naveh NSS, Kavari SL, et al. Cancer predisposition signaling in beckwith-wiedemann syndrome drives wilms tumor development[J]. Br J Cancer, 2024, 130(4): 638-650.
[34]	Abbou S, Klega K, Tsuji J, et al. Circulating tumor DNA is prognostic in intermediate-risk rhabdomyosarcoma: A report from the children's oncology group[J]. J Clin Oncol, 2023, 41(13): 2382-2393.
[35]	Adane B, Alexe G, Seong BKA, et al. STAG2 loss rewires oncogenic and developmental programs to promote metastasis in Ewing sarcoma[J]. Cancer Cell, 2021, 39(6): 827-844.e10. doi: 10.1016/j.ccell.2021.05.007 pmid: 34129824
[36]	Klega K, Imamovic-Tuco A, Ha G, et al. Detection of somatic structural variants enables quantification and characterization of circulating tumor DNA in children with solid tumors[J]. JCO Precis Oncol, 2018, 2018:PO.17.00285.
[37]	Saarinen-Pihkala UM, Parto K, Riikonen P, et al. RALLE pilot: Response-guided therapy for marrow relapse in acute lymphoblastic leukemia in children[J]. J Pediatr Hematol Oncol, 2012, 34(4): 263-270. doi: 10.1097/MPH.0b013e3182352da9 pmid: 22246158
[38]	Zhu GQ, Liu WR, Tang Z, et al. Serial circulating tumor DNA to predict early recurrence in patients with hepatocellular carcinoma: A prospective study[J]. Mol Oncol, 2022, 16(2): 549-561.
[39]	Fu Y, Xu Y, Liu W, et al. Tumor-informed deep sequencing of ctDNA detects minimal residual disease and predicts relapse in osteosarcoma[J]. EClinicalMedicine, 2024, 73: 102697.
[40]	Berko ER, Witek GM, Matkar S, et al. Circulating tumor DNA reveals mechanisms of lorlatinib resistance in patients with relapsed/refractory ALK-driven neuroblastoma[J]. Nat Commun, 2023, 14(1): 2601. doi: 10.1038/s41467-023-38195-0 pmid: 37147298
[41]	Leonetti A, Cervati V, Minari R, et al. Liquid biopsy and 18F-FDG PET/CT derived parameters as predictive factors of osimertinib treatment in advanced EGFR-Mutated NSCLC[J]. Clin Lung Cancer, 2024, 25(8): e436-e45.e9.
[42]	Cabús L, Lagarde J, Curado J, et al. Current challenges and best practices for cell-free long RNA biomarker discovery[J]. Biomark Res, 2022, 10(1): 62. doi: 10.1186/s40364-022-00409-w pmid: 35978416
[43]	Godsey JH, Silvestro A, Barrett JC, et al. Generic protocols for the analytical validation of next-generation sequencing-based ctdna assays: A joint consensus recommendation of the BloodPAC's analytical variables working group[J]. Clin Chem, 2020, 66(9): 1156-1166. doi: 10.1093/clinchem/hvaa164 pmid: 32870995
[44]	Mangum R, Reuther J, Sen Baksi K, et al. Circulating tumor DNA sequencing of pediatric solid and brain tumor patients: An institutional feasibility study[J]. Pediatr Hematol Oncol, 2023, 40(8): 719-738.
[45]	Kramer A, Schuuring E, Vessies DCL, et al. A micro-costing framework for circulating tumor DNA testing in dutch clinical practice[J]. J Mol Diagn, 2023, 25(1): 36-45.
[46]	Keup C, Kimmig R, Kasimir-Bauer S. Combinatorial power of cfDNA, CTCs and EVs in oncology[J]. Diagnostics (Basel), 2022, 12(4):870.
[47]	Liu F, Xiong QW, Wang JH, et al. Roles of lncRNAs in childhood cancer: Current landscape and future perspectives[J]. Front Oncol, 2023, 13: 1060107.
[48]	Werutsky G, Barrios CH, Cardona AF, et al. Perspectives on emerging technologies, personalised medicine, and clinical research for cancer control in Latin America and the Caribbean[J]. Lancet Oncol, 2021, 22(11): e488-e500.

小儿肿瘤中ctDNA的研究进展

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献 48

相关文章 15

编辑推荐

Metrics

本文评价

[1]	张天娇, 宋菲, 由佳鹭, 金雨佳, 孙妍. 肝癌细胞上皮-间质转化中微小RNA通路调控的研究进展[J]. 临床荟萃, 2026, 41(7): 659-667.
[2]	唐佳, 徐一舟, 吴娇, 张健. C反应蛋白-白蛋白-淋巴细胞指数对肺癌患者预后价值的系统评价与meta分析[J]. 临床荟萃, 2026, 41(6): 493-498.
[3]	冯利菲, 王天慧, 吕慧. 血清AFP、AFP-L3、HSP90α对乙肝肝硬化和乙肝相关性肝癌的鉴别价值及其与HBV-DNA载量的关系[J]. 临床荟萃, 2026, 41(6): 505-510.
[4]	赵丹, 杨亚莉, 张志强. 结直肠癌患者外泌体miR-23b、miR-152-3p表达水平及其对预后的预测价值[J]. 临床荟萃, 2026, 41(6): 516-521.
[5]	王天慧, 吕慧, 冯利菲, 陈亚杰. 血清FABP5、SII、VEGF水平与肝癌患者预后的关系分析[J]. 临床荟萃, 2026, 41(5): 399-405.
[6]	施少鑫, 陈雪婷, 庄亦晖, 郭林, 卢仁泉, 许晓峰. 恶性肿瘤患者尿路感染病原菌分布及血糖和尿液分析指标联合检测的应用[J]. 临床荟萃, 2026, 41(5): 406-410.
[7]	刘晓丽, 杨爽, 尹丽, 胡艳, 郑雨萌, 段丽红. 人工智能辅助不同年资医师评估乳腺4类结节[J]. 临床荟萃, 2026, 41(5): 411-416.
[8]	张志源, 夏娟, 李璎芝, 王东辉, 邓文杰, 张琰. 循环肿瘤DNA液体活检在胃癌诊疗中的应用进展[J]. 临床荟萃, 2026, 41(5): 462-467.
[9]	李鑫月, 李世豪, 刘娜, 吴婧, 李美玲, 刘改芳. CC趋化因子配体调控胃癌的研究现状及进展[J]. 临床荟萃, 2026, 41(4): 363-368.
[10]	汤思颖, 贾君萍, 唐雨婷, 郑玉琴, 孔悦. 膳食炎症指数与肺癌风险相关性的meta分析[J]. 临床荟萃, 2026, 41(3): 197-204.
[11]	孟巧, 程春丽. 循环肿瘤DNA在血液系统恶性肿瘤中的研究进展[J]. 临床荟萃, 2026, 41(3): 280-284.
[12]	古丽米热·依力哈木, 姜春晖, 王俭. 基于影像组学预测TERT突变型高级别胶质瘤复发的研究进展[J]. 临床荟萃, 2026, 41(2): 178-182.
[13]	姬如意, 赵礼荣, 刘沙. 血清CTRP12、Lp-PLA2在急性脑梗死患者中的表达及其与颈动脉粥样硬化的关系[J]. 临床荟萃, 2026, 41(1): 33-37.
[14]	陆敏艳, 周莉, 戚志强, 路阳. CTA联合血清TNF-α、IFN-γ对缺血性脑卒中患者颈动脉斑块的诊断价值[J]. 临床荟萃, 2026, 41(1): 38-43.
[15]	韦婷婷, 潘正燕, 冯鲜燕, 龙亚秀. 基于SEER数据库的结直肠癌肝转移危险因素分析:倾向评分匹配研究[J]. 临床荟萃, 2025, 40(9): 816-820.