IDH1 mutations are present in the majority of common adult gliomas but rare in primary glioblastomas.
We screened exon 4 of the gene isocitrate dehydrogenase 1 (NADP+), soluble (IDH1) for mutations in 596 primary intracranial tumors of all major types. Codon 132 mutation was seen in 54% of astrocytomas and 65% of oligodendroglial tumors but in only 6% of glioblastomas (3% of primary and 50% of secondary glioblastomas). There were no mutations in any other type of tumor studied. While mutations in the tumor protein p53 gene (TP53) and total 1p/19q deletions were mutually exclusive, IDH1 mutations were strongly correlated with these genetic abnormalities. All four types of mutant IDH1 proteins showed decreased enzymatic activity. The data indicate that IDH1 mutation combined with either TP53 mutation or total 1p/19q loss is a frequent and early change in the majority of oligodendroglial tumors, diffuse astrocytomas, anaplastic astrocytomas, and secondary glioblastomas but not in primary glioblastomas.
Molecular Histopathology, Level 3, Lab Block, Addenbrooke's Hospital, Box 231, Cambridge CB20QQ, UK. ki212@cam.ac.uk
Koichi
K
Ichimura
Danita M
DM
Pearson
Sylvia
S
Kocialkowski
L Magnus
LM
Bäcklund
Raymond
R
Chan
David T W
DT
Jones
V Peter
VP
Collins
D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D005091:Exons / Q000235:genetics; D005838:Genotype; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D019656:Loss of Heterozygosity; D009154:Mutation / Q000235:genetics*; D009837:Oligodendroglioma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D007521:Isocitrate Dehydrogenase