Mehdi Mohebalizadeh
1 
, Tooba Mohammadi
1, Somayeh Abolhasani
1,2, Zahra Asadi
1, Maryam Kahyaei-Aghdam
1, Negin Mahboubi
1, Rahim Asghari
3,4, Vahid Shafiei-Irannejad
5* , Shahriar Alipour
5,6* 1 Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran
2 Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
3 Hematology, Immune Cell Therapy, and Stem Cell Transplantation Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran
4 Department of Internal Medicine, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
5 Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
6 Department of Clinical Biochemistry and Applied Cell Sciences, Urmia University of Medical Sciences, Urmia, Iran
Abstract
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.