TY - JOUR
T1 - Rapid detection of mutation in isocitrate dehydrogenase 1 and 2 genes using mass spectrometry
AU - Kanamori, Masayuki
AU - Maekawa, Masamitsu
AU - Shibahara, Ichiyo
AU - Saito, Ryuta
AU - Chonan, Masashi
AU - Shimada, Miki
AU - Sonoda, Yukihiko
AU - Kumabe, Toshihiro
AU - Watanabe, Mika
AU - Mano, Nariyasu
AU - Tominaga, Teiji
N1 - Funding Information:
Acknowledgements This work was supported by Grants-in-Aid for Scientific Research (no. 16K10749) from the Japan Society for the Promotion of Science.
Publisher Copyright:
© 2018, The Japan Society of Brain Tumor Pathology.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - The 2016 World Health Organization classification of tumors of the central nervous system was recently revised. Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes and chromosome 1p/19q codeletion are especially important for both the integrated diagnosis and the determination of surgical strategy. To establish a method for intraoperative molecular diagnosis, a simple, rapid method was developed for the measurement of 2-hydroxyglutarate (2-HG), a specific oncometabolite formed in the presence of IDH gene mutation, using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI–MS/MS). This method requires only 10 min to measure the level of 2-HG from tissue preparation to completion of examination. Using this method, the level of 2-HG was analyzed in 105 patients with diffuse infiltrating glioma, and showed that IDH mutated glioma had significantly higher level of 2-HG compared to IDH wild-type glioma. Receiver operating characteristic curve analysis showed the area under the curve, sensitivity, and specificity were 0.9815, 97.5, and 100%, respectively. In contrast, tumor grade and presence of chromosome 1p/19q codeletion in the IDH mutated glioma could not be predicted from the level of 2-HG. Measurement of 2-HG level using LC/ESI–MS/MS can provide rapid and accurate information of mutation status in the IDH gene.
AB - The 2016 World Health Organization classification of tumors of the central nervous system was recently revised. Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes and chromosome 1p/19q codeletion are especially important for both the integrated diagnosis and the determination of surgical strategy. To establish a method for intraoperative molecular diagnosis, a simple, rapid method was developed for the measurement of 2-hydroxyglutarate (2-HG), a specific oncometabolite formed in the presence of IDH gene mutation, using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI–MS/MS). This method requires only 10 min to measure the level of 2-HG from tissue preparation to completion of examination. Using this method, the level of 2-HG was analyzed in 105 patients with diffuse infiltrating glioma, and showed that IDH mutated glioma had significantly higher level of 2-HG compared to IDH wild-type glioma. Receiver operating characteristic curve analysis showed the area under the curve, sensitivity, and specificity were 0.9815, 97.5, and 100%, respectively. In contrast, tumor grade and presence of chromosome 1p/19q codeletion in the IDH mutated glioma could not be predicted from the level of 2-HG. Measurement of 2-HG level using LC/ESI–MS/MS can provide rapid and accurate information of mutation status in the IDH gene.
KW - Glioma
KW - IDH1 and IDH2 genes
KW - Mass spectrometry
KW - Mutation
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U2 - 10.1007/s10014-018-0317-0
DO - 10.1007/s10014-018-0317-0
M3 - Article
C2 - 29671246
AN - SCOPUS:85045680551
VL - 35
SP - 90
EP - 96
JO - Brain Tumor Pathology
JF - Brain Tumor Pathology
SN - 1433-7398
IS - 2
ER -
