title: IDH1 mutation of gliomas with long-term survival analysis.
abstract: A recurrent mutation affecting codon 132 of the isocitrate dehydrogenase 1 (IDH1) gene has been found in ~5% of primary glioblastomas (GBMs), but in >70% of secondary GBMs or oligodendroglial and astrocytic tumors. We investigated IDH1 mutations in a series of 134 brain tumors to determine the prevalence and prognostic impact of IDH1 mutations. We also examined the correlations among histology, p53 and PTEN immunoexpression, MGMT methylation status, 1p 19q co-deletion and EGFR gene amplification. The 134 brain tumors included 41 low-grade oligodendrogliomas (LOs), 47 anaplastic oligodendrogliomas (AOs) and 46 primary GBMs. Data showed that 53.7% (72/134) of cases showed mutations affecting codon 132 of IDH1, including 73.2% of LOs, 82.9% of AOs and three primary GBMs (6.5%). All IDH1 mutations were Arg132His. In a survival analysis, patients with IDH1 mutations had better survival compared to those with wild-type IDH1 (p<0.05) in LOs and AOs, but not in primary GBMs (p=0.587). In addition, in patients with both IDH1 mutation and MGMT methylation, p53 overexpression was a significant poor prognostic factor both in LOs and AOs. However, IDH1 mutation was not correlated with common genetic profiles that affect patient prognosis, including MGMT methylation, 1p 19q co-deletion, PTEN loss and EGFR amplification in LOs, AOs and GBMs. From our results, IDH1 mutation was an independent positive prognostic factor in LOs and AOs, especially in the absence of p53 overexpression.
authors.affiliation: Department of Pathology, Seoul National University Hospital, College of Medicine, Seoul, Republic of Korea.
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Myung
authors.forename: Hwa Jin
authors.initials: HJ
authors.lastname: Cho
authors.forename: Chul-Kee
authors.initials: CK
authors.lastname: Park
authors.forename: Seung-Ki
authors.initials: SK
authors.lastname: Kim
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Phi
authors.forename: Sung-Hye
authors.initials: SH
authors.lastname: Park
mesh_terms: D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics / Q000401:mortality; D019175:DNA Methylation / Q000235:genetics; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D005784:Gene Amplification; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D009154:Mutation; D009837:Oligodendroglioma / Q000235:genetics* / Q000401:mortality; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis; D011379:Prognosis; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D045643:DNA Repair Enzymes