TY - JOUR
T1 - Pyrosequencing of IDH1 and IDH2 mutations in brain tumors and non-neoplastic conditions
AU - Cykowski, Matthew D.
AU - Allen, Richard A.
AU - Fung, Kar Ming
AU - Harmon, Michael A.
AU - Dunn, Samuel T.
PY - 2012/12
Y1 - 2012/12
N2 - The molecular profiling of brain tumors, including testing for MGMT promoter methylation and chromosome 1p/19q deletion, can provide both diagnostic and prognostic information that may guide treatment. Isocitrate dehydrogenase (IDH) mutation testing is a recent addition to this armamentarium of molecular pathology tools that similarly provides both diagnostic (eg, glioma vs. gliosis) and prognostic information. Herein, we describe a pyrosequencing-based approach to IDH1 and IDH2 mutation testing and its application to 139 neoplastic and non-neoplastic central nervous system specimens. Several technical issues encountered in the development of the assay, particularly with regard to the optimization of the sequencing reaction, are described. Mutations in IDH1 codon 132 or IDH2 codon 172 were identified in 31.2% of all screened cases and 46.2% of screened World Health Organization grade I to IV gliomas (n=93), with mutations arising exclusively in grade II to IV oligodendroglial, astrocytic, or mixed oligoastrocytic neoplasms. Examination of the relationship between the mutation status and other pertinent variables demonstrated a significant male predominance among IDH1-mutated gliomas, most notably in grade III to IV astrocytic neoplasms. A significant association between IDH1/IDH2 mutation and 1p/19q deletion was also seen (Kendall τ coefficient=0.26, P=0.018), although several cases with 1p/19q deletion were IDH1/IDH2 wild type.
AB - The molecular profiling of brain tumors, including testing for MGMT promoter methylation and chromosome 1p/19q deletion, can provide both diagnostic and prognostic information that may guide treatment. Isocitrate dehydrogenase (IDH) mutation testing is a recent addition to this armamentarium of molecular pathology tools that similarly provides both diagnostic (eg, glioma vs. gliosis) and prognostic information. Herein, we describe a pyrosequencing-based approach to IDH1 and IDH2 mutation testing and its application to 139 neoplastic and non-neoplastic central nervous system specimens. Several technical issues encountered in the development of the assay, particularly with regard to the optimization of the sequencing reaction, are described. Mutations in IDH1 codon 132 or IDH2 codon 172 were identified in 31.2% of all screened cases and 46.2% of screened World Health Organization grade I to IV gliomas (n=93), with mutations arising exclusively in grade II to IV oligodendroglial, astrocytic, or mixed oligoastrocytic neoplasms. Examination of the relationship between the mutation status and other pertinent variables demonstrated a significant male predominance among IDH1-mutated gliomas, most notably in grade III to IV astrocytic neoplasms. A significant association between IDH1/IDH2 mutation and 1p/19q deletion was also seen (Kendall τ coefficient=0.26, P=0.018), although several cases with 1p/19q deletion were IDH1/IDH2 wild type.
KW - IDH1
KW - IDH2
KW - Pyrosequencing
KW - glioma
KW - isocitrate dehydrogenase
UR - http://www.scopus.com/inward/record.url?scp=84870249020&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870249020&partnerID=8YFLogxK
U2 - 10.1097/PDM.0b013e31825d802b
DO - 10.1097/PDM.0b013e31825d802b
M3 - Article
C2 - 23111198
AN - SCOPUS:84870249020
SN - 1052-9551
VL - 21
SP - 214
EP - 220
JO - Diagnostic Molecular Pathology
JF - Diagnostic Molecular Pathology
IS - 4
ER -