Investigation of HSNF5/INI1 gene mutations in patients with embryonal tumors, which is a subgroup of childhood central nervous system tumors

Objective: In this study, it was aimed to investigate the mutation of a tumor suppressor gene (hSNF5 / INI1) associated with atypical teratoid rabdoid tumor (AT / RT) from embryonal tumors, which is a subgroup of childhood central nervous system tumors. Material and Method: The data of patients with AT / RT diagnosed between 2010 and 2015 in Ege University Medical Faculty were reviewed. Clinical findings and INI1 expression in tumor tissue using immunohistochemical analysis results of were evaluated. In all tumor tissues, all exonic regions of the hSNF5 / INI1 gene were amplified by PCR and after cheching by gel electrophoresis, DNA sequence analysis was performed. The results obtained were compared with the reference genome. The pathogenicity of the detected variants was assessed according to ACMG 2015 criteria. DNA sequencing in peripheral blood was performed in the patients with mutation in tumor tissue. Results: Ten patients were enrolled in the study. 7 of them had AT/RT in central nervous system, 2 in soft tissue and 1 in renal. Of 7 patients who had AT / RT of the central nervous system (CNS), 4 (57%) were girls and 3 (43%) were boys. The median age at diagnosis was 18 months (3 months-12.9 years). 85% of our patients were diagnosed before 36 months. The mean survival time of the patients was 5.8 ( ± 28.7) months. In 4 (57%) of the cases with AT/RT in CNS, the tumor was infratentorial, whereas in 3 (43%) the tumor was supratentorial. The median age at diagnosis was 19 months (16 months- 12,9 years) and the mean survival time was 7.3 (± 5.7) months in patients with tumors located in the supratentorial region. The median age at diagnosis was 17.5 months (3-19 months) and the mean survival time was 23.2 (± 38.5) months in the patients who were followed up for infratentorial tumor. Gross total excision of 2 patients (28.5%) and partial excision of 5 patients (71.4%) were performed in 7 patients who were diagnosed with AT/RT of the CNS. The mean survival time of patients with gross total excision was 43.5 (± 53.7) months and the mean survival time of patients with residual tumor tissue was 5.8 (± 4.7) months. The expression of hSNF5 / INI1 protein that has been examined by immunohistochemical methods in the patients with AT/RT of the CNS, soft tissue and renal rhabdoid tumors was evaluated and loss of protein expression was found in 77% of the patients. All patients with soft tissue and renal rhabdoid tumors showed loss of hSNF5 / INI1 protein expression in tumor tissue. Protein expression was lost in 4 of the 7 patients diagnosed with AT/RT of the CNS, protein expression was completely preserved in one patient, and focally conserved in one patient. In one patient, there was no data about protein expression. The median age at diagnosis was 18 months (3-19 months) and the mean survival time was 3.2 (± 2.6) months in patients with loss of hSNF5 / INI1 protein expression. In the hSNF / INI1 sequence analysis, mutations in tumor tissue were detected in 4 patients. Three of these patients had AT/RT of CNS and one of them had a soft-tissue rabboid tumor. The median age at diagnosis was 19 months (17-19 months) and the mean survival time was 4 (± 2.6) months for patients with AT/RT of CNS with mutations in the hSNF5 / INI1 gene. The median age at diagnosis was 17 months (3 months-12,9 years) and the mean survival time was 25.7 (± 37.1) months in patients with no mutation in hSNF5 / INI1 gene. There was a patient who was diagnosed with soft tissue rhabdoid tumor diagnosis and detected a mutation in the hSNF5 / INI1 gene in the tumor. At the time of diagnosis, the age of the patient is 3.5 months and the survival time is 15 months. The disease was remedied when this work was done. We have not detected mutation in the DNA obtained from the blood of patients who have mutation in the tumor. Parents of mutation-bearing patients were evaluated using the Sanger sequence analysis for the same mutation. It was shown that the parents of the patients did not carry this mutation. Conclusıons: Patients with AT / RT were found to have shorter survival times when mutations in the hSNF5 / INI1 gene were detected in the tumor. For this reason, mutation analysis could be recommended to predict prognosis. The future researchs conducted with larger patient groups is needed to determine the role of molecular analysis in the patients with AT/RT. Unlike previous reports, no germline mutation in the hSNF5 / INI1 gene was detected in any of the patients with AT / RT. This result is thought to be related to the limited number of patients that could be analyzed.