Isocitrate dehydrogenase mutation is frequently observed in giant cell tumor of bone.
Bottom Line: No available treatment is definitively effective in curing GCTB, especially in surgically unresectable cases.The IDH mutations are remarkably specific to arginine 132 (R132) in IDH1 and arginine 172 (R172) or arginine 140 (R140) in IDH2; IDH1/2 mutations are known to convert α-ketoglutarate to oncometabolite R(-)-2-hydroxyglutarate.DNA direct sequencing and subcloning identified IDH mutations of GCTB as IDH2-R172S (16 of 20; 80%).
Affiliation: Department of Regional Innovation, Tohoku University Graduate School of Medicine, Sendai, Japan.Show MeSH
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Mentions: Polymerase chain reaction was carried out using DNA samples obtained from tissue microarray. No IDH1 mutation was observed in 20 samples (Table1). In contrast, 13 of 20 (65%) GCTB samples possessed IDH2 mutations. It is noteworthy that all 13 IDH2 mutations were of IDH2-R172S (AGG > AGT; Fig.1d,e), which is also frequently observed in osteosarcomas and chondrosarcomas.11,12 After subcloning of PCR products, 3 of 6 (50%) GCTB samples were shown to possess IDH2-R172S (Fig.2, Table1). In total, 16 of 20 (80%) GCTB samples were shown to possess IDH2-R172S (Table1). In 5 of 20 (25%) GCTB patients, IDH2-H175Y (CAT > TAT) mutations were detected (Fig.3a, Table1), although IDH2-H175Y mutation was not recognized by MsMab-1 in Western blot analyses (Fig.3b). The U2 OS IDH2-R172S cells produced 99.4 μmol/L of oncometabolite 2-HG, whereas U2 OS IDH2-H175Y, U2 OS IDH2-WT, and U2 OS cells produced 1.7, 1.3, and 1.6 μmol/L 2-HG, respectively (Fig.3b).
Affiliation: Department of Regional Innovation, Tohoku University Graduate School of Medicine, Sendai, Japan.