GCT-13. Kras Mutation in Pediatric Intracranial Germ Cell Tumors

Abstract

BACKGROUND: Intracranial germ cell tumors (IGCTs) are rare, highly curable neoplasms. KRAS is a gene in the KIT/RAS signaling pathway, and KRAS mutations were reported in patients diagnosed with IGCTs. OBJECTIVES: To describe clinicopathologic, molecular features of KRAS mutation and treatment outcome of children diagnosed with IGCTs. METHODS: A retrospective review in patients diagnosed with IGCTs at Department of Pediatrics, King Chulalongkorn Memorial Hospital from 2007 to 2019. DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue for the molecular study. Identifies mutations in codon 12,13 and 61 of the KRAS gene was performed by using the real-time PCR technique of the Cobas® test and pyrosequencing method. RESULTS: Eighteen patients were diagnosed with IGCTs (11 males and seven females). Age ranged from 5 to 14 years (median 10.5 years). The diagnosis was germinoma and non-germinomatous IGCTs in 9 patients each. Elevated markers were revealed in approximately 25% of patients. Four patients (2 patients with germinoma and 2 with non-germinomatous IGCTs) had leptomeningeal involvement. All patients underwent tumor biopsy and received neoadjuvant chemotherapy. Radiotherapy was given in 16 patients and craniospinal radiation (CSI) was given only in leptomeningeal metastasis. With the median follow-up of 26 months, overall survival is 88.9% in germinomas and 37% in non-germinomatous IGCTs. Mutation of the KRAS gene was detected by pyrosequencing technique in one patient. The mutation located at codon 61, frequency 38.3% units, nucleotide substitution CAA > CTA and amino acid substitution was Q61L. The patient who carries mutant gene was diagnosed germinomatous germinoma with CSF metastasis and eventually died from treatment-related toxicity. CONCLUSIONS: Our study revealed treatment outcomes of IGCTs in Thai children. We describe KRAS codon 61 mutation in metastasis germinoma patients with poor outcome, support KRAS codon 61 mutation (Q61L) may have a clinical correlation in IGCTs.