title: Expanding the spectrum of IDH1 mutations in gliomas.
abstract: Mutations in isocitrate dehydrogenase -1 or -2 (IDH1 or IDH2) are found in the majority of WHO grade II and III diffuse gliomas and secondary glioblastomas. IDH mutation screening is rapidly becoming part of the routine pathological work up of human brain tumors, providing both diagnostic and prognostic information. Here, we characterize four rare and novel IDH1 mutations identified in surgical human glioma samples: two instances of an IDH1 p.R132S mutation caused by a previously undescribed dinucleotide deletion/insertion mutation, a novel homozygous somatic IDH1 p.R132L mutation, and an IDH1 p.R100Q mutation. Characterization of novel and rare IDH mutations may provide additional insight into the mechanisms of mutant IDH in neoplasia. Furthermore, given the clinical import of IDH status, these results highlight the need for comprehensive mutation screening, beyond the targeted identification of common pathogenic variants.
authors.affiliation: Department of Neuropathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: Ruta
authors.initials: R
authors.lastname: Gupta
authors.forename: Simon
authors.initials: S
authors.lastname: Flanagan
authors.forename: Cheryl C Y
authors.initials: CC
authors.lastname: Li
authors.forename: Maggie
authors.initials: M
authors.lastname: Lee
authors.forename: Brindha
authors.initials: B
authors.lastname: Shivalingham
authors.forename: Sanaz
authors.initials: S
authors.lastname: Maleki
authors.forename: Helen R
authors.initials: HR
authors.lastname: Wheeler
authors.forename: Michael E
authors.initials: ME
authors.lastname: Buckland
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005910:Glioma / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human