ATRT-32. PREPARATION OF GENETIC TESTING SYSTEM OF AT/RT FOR PEDIATRIC CANCER PREDISPOSITION PROGRAM

Abstract Atypical teratoid rhabdoid tumors (AT/RTs) are highly aggressive embryonal CNS tumors. Up to one-third of AT/RTs are reported to have germline mutation and/or deletion of SMARCB1/hSNF5. In accordance with the increased understanding for pediatric cancer predisposition syndrome, the needs for genetic counseling and testing is expanding. And next generation suquencing technique is inevitable for these genotyping. So we start to prepare genetic testing system of AT/RT for future pediatric cancer predisposition program. Proior to the genetic testing, pretest counseling is performed for each patient/family. Informed consent was obtained according to the institutional ethical review board. Genomic DNA was isolated from the patient’s periphera blood, and somatic DNA was extracted from frozen tissues or FFPE samples. Genetic analysis of the SMARCB1 coding sequence was performed by Sanger method. Deletion of SMARCB1 is examined by quantitative analysis of each exon with droplet digital PCR (ddPCR). SNP array analysis is also tried if frozen sample is available. Three AT/RT patients and one rhabdoid tumor patient received genetic testing. None of them had germline mutation. In an infant ATRT, Sanger sequence analysis revealed frameshift mutation (c649-650delAT). Also, ddPCR showed uniparenteral heterodisomy (UPD). In another AT/RTs, copy number decrease and UPD over whole region of SMARCB1, or exon 3 deletion are recognized respectively. Rhabdoid tumor case had nonsense mutation (c610C>T). Although most of AT/RT should have biallelic mutation, false negative could happen due to less tumor cells obtained in those samples. Enlightenment for sampling and accumulation for testing would be important.