Liquid biopsy is a noninvasive means to diagnose, identify targetable mutations, and monitor disease progression, recurrence, and treatment response in cancer. It can be done with circulating tumor cells, microRNAs, exosomes, and cell-free DNA (cfDNA).¹ cfDNA can identify specific tumor mutations, referred to as circulating tumor DNA (ctDNA). In uveal melanoma, initiating mutations are mutually exclusive and are recognized as GNAQ, GNA11, CYSLTR2, and PLCB4.^1,2 These can be used as a marker of melanocytic tumor origin but not necessarily as signifiers of malignancy, because choroidal nevi also carry these alterations. More pertinent to uveal melanoma and its prognosis are the cooperating driver mutations,^1,2 which consist of EIF1AX, SF3B1, and BAP1 in order of increasing potential risk for future metastases. These findings suggest a need for a noninvasive, easily repeatable measure of these driver mutations, one that can circumvent the morbidity of an invasive intraocular procedure and can avoid reliance on a coordinated, anesthetized procedure for specimen retrieval. We report here the potential utility of plasma cfDNA for uveal melanoma: unlike published reports that only interrogate limited exons in initiating mutations,^1-3 our assay detects a panel of 129 oncogenes⁴ including both initiating and mutations driving malignant transformation of uveal melanoma. In our case, the findings suggested that the cfDNA assay potentially heralded the diagnosis of metastatic uveal melanoma, stratified appropriate confirmatory imaging based on the driver mutations, and led to an earlier diagnosis.

液体活检是一种无创手段，用于诊断、识别靶向突变以及监测癌症的疾病进展、复发和治疗反应。它可以利用循环肿瘤细胞、microRNA、外泌体和无细胞 DNA (cfDNA) 来完成。¹ cfDNA可以识别特定的肿瘤突变，称为循环肿瘤DNA（ctDNA）。在葡萄膜黑色素瘤中，起始突变是相互排斥的，被识别为GNAQ、GNA11、CYSLTR2和PLCB4。^{1,2 _}这些可以用作黑素细胞肿瘤起源的标志物，但不一定作为恶性肿瘤的标志，因为脉络膜痣也携带这些改变。与葡萄膜黑色素瘤及其预后更相关的是协同驱动突变^{1 ,2}，其中包括EIF1AX、SF3B1和BAP1以增加未来转移的潜在风险。这些发现表明需要对这些驱动突变进行非侵入性、易于重复的测量，这种测量可以避免侵入性眼内手术的发病率，并可以避免对标本检索的协调麻醉程序的依赖。我们在此报告血浆 cfDNA 对于葡萄膜黑色素瘤的潜在效用：与仅询问启动突变中有限外显子的已发表报告不同，^{1 -3}我们的检测检测到一组 129 个癌基因⁴包括葡萄膜黑色素瘤恶性转化的起始和驱动突变。在我们的病例中，研究结果表明，cfDNA 检测可能预示着转移性葡萄膜黑色素瘤的诊断，根据驱动突变对适当的验证性成像进行分层，并导致早期诊断。