Detection of 2-Hydroxyglutarate by 3.0-Tesla Magnetic Resonance Spectroscopy in Gliomas with Rare IDH Mutations: Making Sense of “False-Positive” Cases
Manabu Natsumeda,
Hironaka Igarashi,
Ramil Gabdulkhaev,
Haruhiko Takahashi,
Kunio Motohashi,
Ryosuke Ogura,
Jun Watanabe,
Yoshihiro Tsukamoto,
Kouichirou Okamoto,
Akiyoshi Kakita,
Tsutomu Nakada,
Yukihiko Fujii
Affiliations
Manabu Natsumeda
Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata 951-8122, Japan
Hironaka Igarashi
Center for Integrated Brain Sciences, Brain Research Institute, Niigata University, Niigata 951-8585, Japan
Ramil Gabdulkhaev
Department of Pathology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan
Haruhiko Takahashi
Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata 951-8122, Japan
Kunio Motohashi
Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata 951-8122, Japan
Ryosuke Ogura
Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata 951-8122, Japan
Jun Watanabe
Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata 951-8122, Japan
Yoshihiro Tsukamoto
Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata 951-8122, Japan
Kouichirou Okamoto
Department of Translational Research, Brain Research Institute, Niigata University, Niigata 951-8585, Japan
Akiyoshi Kakita
Department of Pathology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan
Tsutomu Nakada
Center for Integrated Brain Sciences, Brain Research Institute, Niigata University, Niigata 951-8585, Japan
Yukihiko Fujii
Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata 951-8122, Japan
We have previously published a study on the reliable detection of 2-hydroxyglutarate (2HG) in lower-grade gliomas by magnetic resonance spectroscopy (MRS). In this short article, we re-evaluated five glioma cases originally assessed as isocitrate dehydrogenase (IDH) wildtype, which showed a high accumulation of 2HG, and were thought to be false-positives. A new primer was used for the detection of IDH2 mutation by Sanger sequencing. Adequate tissue for DNA analysis was available in 4 out of 5 cases. We found rare IDH2 mutations in two cases, with IDH2 R172W mutation in one case and IDH2 R172K mutation in another case. Both cases had very small mutant peaks, suggesting that the tumor volume was low in the tumor samples. Thus, the specificity of MRS for detecting IDH1/2 mutations was higher (81.3%) than that originally reported (72.2%). The detection of 2HG by MRS can aid in the diagnosis of rare, non-IDH1-R132H IDH1 and IDH2 mutations in gliomas.
