The Preliminary Study Of The Role Of ATRX Gene In Neurobalstoma

Objective:Neuroblastoma (NB), which orginates from the sympathoadrenal lineage of neural crest during the embryonic period, is one of the most common extracranial malignant solid tumors in children. The characteristic features of neuroblastoma are high degree malignancy, early multiple metastases, easy resistance to chemotherapy and high rate of recurrence. In recent studies, ATRX protein was found the expression level increased with the degree of neurons differentiation. ATRX mutations may play an important role in the progression of the central nervous system. So we speculate that ATRX gene mutation may closely related to the development and progression of neuroblastoma. The proteins encoded by the interaction of the ATRX gene mutation play a lot of roles in the mechanism of Alternative Lengthening of Telomeres. The ATRX gene mutation may play an important role in the progression of neuroblastoma by the mechanism of Alternative Lengthening of Telomeres. In this study, we aimed to elucidate the expression of ATRX protein and the alternative lengthening of telomeres mechanism in NBs and explore and mechanism the roles of ATRX gene in the genesis and development of NB.Methods:The expression of ATRX protein was examined in52cases of neuroblastomas(NBs) and in17cases of ganglioneuromas(GNs) by the method of immunohistochemistry technique. The expression of ALT was examined in52cases of NBs by the technique of fluorescence in situ hybridization. We want to detect the relationships between expression of ATRX protein and clinical variables including tumor differentiation, clinical stage and prognosis. We aimed to elucidate the expression of ATRX protein in the development and progression of NBs. The comparison of expression of ATRX protein in differentiations of NBs was performed with the Kruskal Wallis H Test. Mann-Whitney Test was performed in the comparison of the expression of ATRX protein in different stages and between NBs and GNs. The expression of ATRX protein and ALT were performed with the x2Test. The method of Kaplan Meier was used to calculate survival rates. The single factor analysis was performed by the Log-Rank Test. All data were processed with SPSS for windows software version17.0, the level of significance was set at0.05of two-sided test.Results:1. In52cases of neuroblastoma, the positive rate of ALT was40.38%and the positive rate of ATRX protein was46.15%. In17cases of ganglioneuromas, the positive rate of ATRX protein was88.24%.2. The expression of ATRX protein showed significantly lower level in early NBs (Ⅰ, Ⅱ stage) than in advanced NBs(Ⅲ, Ⅳ stage)(P=0.004). The expression of ATRX protein was significantly higher in the differentiating NBs than undifferentiated NBs and poorly differentiated NBs (P=0.019). The expression of ATRX protein was significantly higher in GNs than in NBs (P=0.000); Kaplan-Meier curve showed that ATRX-positive NBs whose median survival was52months had a higher survival rate than that ATRX-negative NBs whose median survival was31months (P=0.001).3. The expression of ALT in the ATRX-negative NBs was higher than in the ATRX-positive NBs (P=0.036)Conclusions:1. The overexpression of ATRX protein is closely related to the differentiation of neuroblastoma and low INSS. The NB patients who had the expression of ATRX protein got good prognosis. The ATRX protein has antitumor effect in neuroblastoma. The expression of ATRX protein may be a good prognostic factor and play a role in the spontaneous differentiation in neuroblastoma.2. The ATRX protein deficiency was closely related with the expression of the Alternative Lengthening of Telomeres in neurobalstoma. The ATRX protein deficiency may play an important role in the genesis and development, progression and development of neuroblastoma by activating the mechanism of Alternative Lengthening of Telomeres.