文章：

早期原发性皮肤黑色素瘤组织学分期与肿瘤源性及游离DNA分子改变的相关性分析

Correlation Analyses between Histological Staging and Molecular Alterations in Tumor-Derived and Cell-Free DNA of Early-Stage Primary Cutaneous Melanoma

原文发布日期：25 October 2023

DOI: 10.3390/cancers15215141

类型: Article

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英文摘要：

Here, we investigate the correlation and statistical analyses between histological staging and molecular alterations in tumor-derived (tdDNA) and cell-free DNA (cfDNA) obtained from early-stage primary cutaneous melanoma (PCM) patients using digital PCR (dPCR) for the detection of theBRAFp.V600E somatic pathogenic variant. In the prospective study, a total of 68 plasma and paired tdDNA samples, and in the retrospective cohort, a total of 100 tdDNA samples were analyzed using dPCR and reverse hybridization StripAssay. The Breslow depth (BD) and Clark level were applied to categorize the study population. Our results demonstrate that dPCR is a highly sensitive and specific method for the detection ofBRAFp.V600E somatic variants in cfDNA samples from PCM patients. A strong correlation was detected between BD and cfDNA concentration in all mutant and negative cases, between the tdDNA concentration and the tumor-derived variant allele frequency (VAF) ofBRAFp.V600E, between the tdVAF and the cfVAF in all cases, and between the cfDNA and cfVAF in mutant cases. The tdVAF and cfVAF ofBRAFp.V600E and cfDNA concentration were the highest in Clark’s V category. The cfDNA concentration was statistically significantly higher in Clark’s III, IV, and V groups compared to cases with a better prognosis. It can also be explained by the fact that cases with a more advanced stage classification release more cfDNA into the peripheral circulation.

摘要翻译： 

本研究采用数字PCR（dPCR）技术检测早期原发性皮肤黑色素瘤（PCM）患者肿瘤源性DNA（tdDNA）与游离DNA（cfDNA）中BRAF p.V600E体细胞致病性变异，系统分析了组织学分期与分子改变之间的相关性及统计学特征。在前瞻性研究中，我们通过dPCR及反向杂交条带检测技术分析了68例血浆及配对tdDNA样本；回顾性队列中则检测了100例tdDNA样本。研究人群根据Breslow厚度（BD）和Clark分级进行分层。结果表明，dPCR对PCM患者cfDNA中BRAF p.V600E体细胞变异的检测具有高灵敏度和特异性。研究发现：所有突变型与阴性病例中BD与cfDNA浓度呈强相关；tdDNA浓度与肿瘤源性BRAF p.V600E变异等位基因频率（VAF）显著相关；所有病例中tdVAF与cfVAF高度一致；突变病例中cfDNA浓度与cfVAF密切关联。Clark V级病例的BRAF p.V600E tdVAF、cfVAF及cfDNA浓度均达最高值。与预后较好组相比，Clark III、IV、V级组的cfDNA浓度具有统计学显著升高，这可由疾病分期更晚的病例向外周循环释放更多cfDNA的现象所解释。

原文链接：

Correlation Analyses between Histological Staging and Molecular Alterations in Tumor-Derived and Cell-Free DNA of Early-Stage Primary Cutaneous Melanoma