Abstract
Retinoblastoma(RB)is the most common primary intraocular malignancy in children,originating from retinal photoreceptor precursor cells.It is highly malignant and can be life-threatening if not treated promptly.Currently,the diagnosis of RB mainly relies on clinical features,such as fundus examination,and imaging findings,including ultrasound,CT,and MRI.Prognostic evaluation is mainly based on disease staging and the patient's response to treatment.Direct tumor biopsy is deemed an absolute contraindication,particularly in patients requiring eye preservation,due to the risk of tumor dissemination.Therefore,identifying alternative biomarkers that can accurately reflect the tumor status holds immense significance for the diagnosis,treatment decision-making,efficacy monitoring,and prognostic assessment of RB.In recent years,circulating tumor DNA(ctDNA),as a key marker in liquid biopsy,has been increasingly investigated in the context of RB.ctDNA refers to DNA fragments released into body fluids during tumor cell apoptosis or necrosis.These fragments carry tumor-specific genetic variations that can mirror molecular characteristics such as gene mutations and copy number variations.The detection methods for ctDNA mainly encompass PCR-related technologies[e.g.,quantitative real-time PCR(qPCR),digital PCR(dPCR)]and next-generation sequencing(NGS)technology.Among them,dPCR has a sensitivity of detecting a mutation frequency as low as 0.01%,while NGS enables comprehensively detection of genetic variations.In clinical applications,ctDNA in body fluids such as aqueous humor,blood,and cerebrospinal fluid(CSF)has shown its value:Aqueous humor ctDNA,with its high content and low interference,can accurately reflect tumor's molecular characteristics.Blood ctDNA is readily accessible and is suitable for monitoring advanced or metastatic RB;CSF ctDNA can be used to monitor central nervous system metastasis.Specifically,ctDNA has exhibited potential application value in early diagnosis of RB(supplementing the limitations of traditional methods),prognostic evaluation(RB1 gene mutation types and tumor fraction(TFx)are associated with prognosis),treatment response monitoring(dynamic changes reflect efficacy and drug resistance),and prenatal diagnosis(enabling non-invasive detection of genetic risks).This article reviews the detection methods of ctDNA in RB,research characteristics in different body fluids,clinical applications,and research progress.It also discusses the challenges it faces,such as insufficient detection sensitivity,small sample size,and a lack of standardization.Furthermore,it looks forward to development directions,including technical optimization,large-scale clinical trials,and multi-omics integration,with the aim of providing new insights for the precise diagnosis and treatment of RB.关键词
视网膜母细胞瘤/循环肿瘤DNA/液体活检/诊断/预后/治疗监测Key words
retinoblastoma/circulating tumor DNA/liquid biopsy/diagnosis/prognosis/treatment monitoring分类
医药卫生
