Identification of a novel variant In a case with adamantinomatous craniopharyngioma in IDH2 gene

Isocitrate dehydrogenase one and two genes are homologous metabolic isozymes, and mutation of these genes generates a neomorphic enzyme, which can lead to the abnormal accumulation of two hydroxyglutarate which promotes tumorigenesis. Isocitrate dehydrogenase one mutation is an early event in brain tumorigenesis, over seventy percent of grade two and grade three gliomas have mutation in this gene. The molecular detection of these mutations have became standard practice in many institutions, and has proven useful in the clinical management of gliomas. We have sequenced by capillary method brain tumor samples for Isocitrate dehydrogenase two mutations. In a case of a patient from Yemen with adamantinomatous craniopharyngioma a novel missense mutation in Isocitrate dehydrogenase two codon 472C to T, amino acid changed Pro158Ser was detected by capillary sequencing. This novel mutation was not reported in Central Nervous System tumors so far. However, this variant was reported in a case of pancreatic ductal adenocarcinoma only.For Sanger sequencing, the FFPE samples were, collected, the nucleic acid extraction was performed using Qiagen kit. Investigation of mutations in exon 4 of Isocitrate dehydrogenase two was done as reported previously by using primers to flank variants in this gene. For this purpose a 288 base pairs sequence with the entire exon four was amplified using forward primer within intron 3 and a reverse primer within intron 4. PCR products were purified using Agencourt Ampure magnetic beads kit. Big Dye reaction products were purified, then the sequencing was done on ABI 3500 Genetic Analyzer.References.Patel KP, Barkoh BA, Chen Z, others. Journal of Molecular Diagnostics. 2011, 13, 678.van den Bent MJ, Dubbink HJ, Marie Y, others. Clin Cancer Research. 2010, 16, 1597.Wartenberg M, Cibin S, Zlobec I, others. Clinical Cancer Research. 2018, 24, 1.Yan H, Parsons DW, Jin G, others. New England Journal of Medicine. 2009, 360, 765.