Maad Rayan Publishing Company Biomedicine Advances 3080-0382 2 2 2025 04 01 Cell-free DNA as a diagnostic method in patients with neuroblastoma: A systematic review 52 60 10.34172/bma.20 EN Mehdi Mohebalizadeh https://orcid.org/0000-0001-9062-4869 Tooba Mohammadi Somayeh Abolhasani Zahra Asadi Maryam Kahyaei-Aghdam Negin Mahboubi Rahim Asghari Vahid Shafiei-Irannejad https://orcid.org/0000-0003-2088-8986 Shahriar Alipour https://orcid.org/0000-0002-2202-9598 Journal Article 10.34172/bma.20 2025 01 10 2025 03 15 This systematic review aims to summarize circulating cell-free DNA (cfDNA) levels and their detection methods for early detection of neuroblastoma with less invasive procedures. After determining the search keywords, including neuroblastoma and cfDNA, these words were searched using MeSH and free keywords in databases. Our results also showed that the diagnostic methods, the time of isolation protocols, and sampling techniques were different in all studies based on extraction kits. The qPCR method was the most used in detecting the gene segments. Samples were obtained from peripheral blood and bone marrow. MYCN amplification was the most seen genetic alteration; ALK, NSE/ (LINE-1), RET, RASSF1A, and APC mutations were often observed. On the clinical scale, patients with higher levels of cfDNA were prone to progressed stages or recurrence of the disease in recovered patients, as some studies have shown that people with recent neuroblastoma had higher levels of cfDNA than those with long-term disease. In conclusion, cfDNA amplification can be a concern in neuroblastoma. It was additionally found that cfDNA ranges in several studies were related to the disorder stage, as some have proven that people with the latest neuroblastoma had higher ranges of cfDNA than those with long-term disease.