PDF(Pubmed)
Abstract：
Medullary Thyroid Carcinoma (MTC) is a rare neuroendocrine tumour whose diagnosis includes evaluating calcitonin serum levels, which can present fluctuations unrelated to MTC. Here, we investigated circulating DNA fragmentation and methylation changes as potential biomarkers using ddPCR on cell-free DNA (cfDNA) isolated from the plasma of MTC patients. For cfDNA fragmentation analysis, we investigated the fragment size distribution of a gene family and calculated short fragment fraction (SFF). Methylation analyses evaluated the methylation levels of CG_16698623, a CG dinucleotide in the MGMT gene that we found hypermethylated in MTC tissues by analyzing public databases. The SFF ratio and methylation of CG_16698623 were significantly increased in plasma from MTC patients at diagnosis, and patients with clinical remission or stable disease at follow-up showed no significant SFF difference compared with healthy subjects. Our data support the diagnostic value of cfDNA traits that could enable better management of MTC patients.
摘要：
甲状腺髓样癌（MTC）是一种罕见的神经内分泌肿瘤，其诊断包括评估降钙素血清水平，这可能会出现与MTC无关的波动。这里,我们使用ddPCR对从MTC患者血浆中分离的无细胞DNA(cfDNA)进行了循环DNA片段化和甲基化变化作为潜在生物标志物的研究.对于cfDNA片段分析，我们调查了基因家族的片段大小分布并计算了短片段分数（SFF）。甲基化分析评估了CG_16698623(MGMT基因中的CG二核苷酸)的甲基化水平,我们通过分析公共数据库在MTC组织中发现了超甲基化。诊断时，MTC患者血浆中CG_16698623的SFF比率和甲基化显著增加，与健康受试者相比，临床缓解或病情稳定的患者在随访时的SFF差异无统计学意义。我们的数据支持cfDNA特征的诊断价值，可以更好地管理MTC患者。
