恶性黑色素瘤（MM）以其丰富的基因改变和快速转移的趋势而闻名。新型血浆生物标志物的鉴定可以增强非侵入性诊断和疾病监测。最初，我们使用 MLPA (gDNA) 和 ddPCR (ctDNA) 分析检查了 CDK 基因（CDKN2A、CDKN2B、CDK4）中的拷贝数变异 (CNV)。随后，使用低覆盖率全基因组测序 (lcWGS) 来识别血浆样本中最常见的 CNV，然后对所选生物标志物进行 ddPCR 验证。在 33.3% 的 FFPE 样本中发现了 CDK 基因的 CNV 改变（仅限 Clark IV、V）。在多发性骨髓瘤血浆中检测到相同基因，无论是与健康血浆相比还是在手术前与手术后血浆之间均没有显着性。测序数据显示最常见的 CNV 发生在 6q27、4p16.1、10p15.3、10q22.3、13q34、18q23、20q11.21-q13.12 和 22q13.33。使用 2 种解释模型通过 ddPCR 验证了四个选定基因（KIF25、E2F1、DIP2C 和 TFG）中的 CNV。模型 1 中 54% 的样本与 lcWGS 结果一致，模型 2 中这一比例为 46%。尽管 CDK 基因尚未被证明是合适的 CNV 液体活检生物标志物，但 lcWGS 定义了最常受 CNV 影响的染色体区域。在选定的基因中，DIP2C 显示出进一步分析的潜力。© 2024。作者。

Malignant melanoma (MM) is known for its abundance of genetic alterations and a tendency for rapid metastasizing. Identification of novel plasma biomarkers may enhance non-invasive diagnostics and disease monitoring. Initially, we examined copy number variations (CNV) in CDK genes (CDKN2A, CDKN2B, CDK4) using MLPA (gDNA) and ddPCR (ctDNA) analysis. Subsequently, low-coverage whole genome sequencing (lcWGS) was used to identify the most common CNV in plasma samples, followed by ddPCR verification of chosen biomarkers. CNV alterations in CDK genes were identified in 33.3% of FFPE samples (Clark IV, V only). Detection of the same genes in MM plasma showed no significance, neither compared to healthy plasmas nor between pre- versus post-surgery plasma. Sequencing data showed the most common CNV occurring in 6q27, 4p16.1, 10p15.3, 10q22.3, 13q34, 18q23, 20q11.21-q13.12 and 22q13.33. CNV in four chosen genes (KIF25, E2F1, DIP2C and TFG) were verified by ddPCR using 2 models of interpretation. Model 1 was concordant with lcWGS results in 54% of samples, for model 2 it was 46%. Although CDK genes have not been proven to be suitable CNV liquid biopsy biomarkers, lcWGS defined the most frequently affected chromosomal regions by CNV. Among chosen genes, DIP2C demonstrated a potential for further analysis.© 2024. The Author(s).