Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Department of Ophthalmology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Invest Ophthalmol Vis Sci. 2023 Oct 3;64(13):35. doi: 10.1167/iovs.64.13.35.
Uveal melanoma (UM) is a tumor of the eye that metastasizes in approximately half of cases. Prognostic testing requires accessibility to tumor tissue, which is usually not available with eye-preserving therapies. Noninvasive approaches to prognostic testing that provide valuable information for patient care are therefore needed. The aim of this study was to evaluate the use of circulating cell-free plasma DNA analysis in UM patients undergoing brachytherapy.
The study recruited 26 uveal melanoma patients referred to the department between February and October 2020. Blood samples were collected at various time points before, during, and after treatment, and deep amplicon sequencing was used to identify oncogenic variant alleles of the GNAQ and GNA11 genes, which serve as indicators for the presence of circulating tumor DNA (ctDNA).
The results showed that all patients were ctDNA negative before brachytherapy. In 31% of patients, ctDNA was detected during therapy. The variant allele fraction of GNAQ or GNA11 alleles in ctDNA positive samples ranged from 0.24% to 2% and correlates with the largest basal diameter and thickness of the tumor.
The findings suggest that brachytherapy increases the presence of tumor DNA in the plasma of UM patients. Thus ctDNA analysis may offer a noninvasive approach for prognostic testing. However, efforts are still required to lower the limit of detection for tumor-specific genetic alterations.
葡萄膜黑色素瘤（UM）是一种眼部肿瘤，约有一半的病例会发生转移。预后检测需要获取肿瘤组织，而这在保眼治疗中通常无法实现。因此，需要一种非侵入性的预后检测方法，为患者提供有价值的信息。本研究旨在评估在接受近距离放射治疗的 UM 患者中使用循环无细胞血浆 DNA 分析的效果。
该研究招募了 2020 年 2 月至 10 月间在该科室就诊的 26 名葡萄膜黑色素瘤患者。在治疗前、治疗中和治疗后各个时间点采集血液样本，并使用深度扩增子测序来鉴定 GNAQ 和 GNA11 基因的致癌变异等位基因，这些基因是循环肿瘤 DNA（ctDNA）存在的标志物。
结果显示，所有患者在近距离放射治疗前均为 ctDNA 阴性。在 31%的患者中，在治疗期间检测到了 ctDNA。ctDNA 阳性样本中 GNAQ 或 GNA11 等位基因的变异等位基因分数为 0.24%至 2%，与肿瘤的最大基底直径和厚度相关。
这些发现表明，近距离放射治疗会增加 UM 患者血浆中肿瘤 DNA 的存在。因此，ctDNA 分析可能为预后检测提供一种非侵入性方法。然而，仍需要努力降低肿瘤特异性遗传改变的检测下限。
