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BACKGROUND: Intracranial germ cell tumors (iGCTs) are the second most common CNS tumors in patients under 14 years old in Japan. But, their molecular genetic profile is largely unknown. METHODS: We have analyzed a total of 198 germ cell tumors (GCTs) including 133 iGCTs (69 pure germinomas, 56 non-germinomatous GCTs and 8 metastatic tumors) as well as 65 testicular germ cell tumors (tGCTs) (39 seminomas and 26 non-seminoma GCTs) were collected from 13 centers participating in the Intracranial Germ Cell Tumor Consortium in Japan. Somatic mutations in all coding exons were investigated by whole exome sequencing (WES) using SureSelectXT Human All Exon v4 and a GAIIx or HiSeq 2000 system in 41 tumors and the matched normal DNAs. Targeted sequencing with a set of custom made PCR primers was performed using either an IonTorrent PGM or Proton System. The results were integrated with the patients' clinical information that was available for 124 iGCT patients. RESULTS: On average, 15.4 non-synonymous somatic mutations were observed in each tumor, ranging from 1 to 140 by WES in 41 iGCTs. MTOR was the second most frequently mutated in both iGCTs (9 cases, 7%) and tGCTs (6%). Collectively, the genes involved in the PI3K/MTOR pathway (e.g., MTOR, PTEN) were mutated in 13% of all GCTs. Clinical parameters of the 9 iGCTs with MTOR mutation were: median age of onset = 15 years old; 7 males and 2 females; 5 germinomas, 3 teratomas and one yolk sac tumor; 5 basal ganglia tumors, 2 pineal tumors, one neurohypophyseal tumor and a medulla oblongata tumor. Age, sex, histology and clinical behavior are within the scope of iGCT except for extraordinary high frequency of basal ganglia GCTs. CONCLUSIONS: iGCTs with MTOR mutation are frequent in iGCTs in basal ganglia. SECONDARY CATEGORY: Pediatrics.

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