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Isocitrate dehydrogenase mutation is frequently observed in giant cell tumor of bone.

Kato Kaneko M, Liu X, Oki H, Ogasawara S, Nakamura T, Saidoh N, Tsujimoto Y, Matsuyama Y, Uruno A, Sugawara M, Tsuchiya T, Yamakawa M, Yamamoto M, Takagi M, Kato Y - Cancer Sci. (2014)

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%).

View Article: PubMed Central - PubMed

Affiliation: Department of Regional Innovation, Tohoku University Graduate School of Medicine, Sendai, Japan.

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Isocitrate dehydrogenase 2 (IDH2)-H175Y (CAT > TAT) mutations were not detected by MsMab-1, a multispecific anti-IDH1/2 mAb. (a) DNA direct sequencing was carried out against bone sample no. 19. (b) Total cell lysate from U-2 OS osteosarcoma cells expressing IDH2 wild-type-PA tag (WT, lane 1) and IDH2 mutants (lane 2, IDH2-R172S-PA tag; lane 3, IDH2-H175Y-PA tag) were electrophoresed, and Western blotted using MsMab-1 or anti-PA tag (NZ-1). Production of oncometabolite R(-)-2-hydroxyglutarate (2-HG) was observed in IDH2-R172S, but not in IDH2-H175Y or IDH2-WT.
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fig03: Isocitrate dehydrogenase 2 (IDH2)-H175Y (CAT > TAT) mutations were not detected by MsMab-1, a multispecific anti-IDH1/2 mAb. (a) DNA direct sequencing was carried out against bone sample no. 19. (b) Total cell lysate from U-2 OS osteosarcoma cells expressing IDH2 wild-type-PA tag (WT, lane 1) and IDH2 mutants (lane 2, IDH2-R172S-PA tag; lane 3, IDH2-H175Y-PA tag) were electrophoresed, and Western blotted using MsMab-1 or anti-PA tag (NZ-1). Production of oncometabolite R(-)-2-hydroxyglutarate (2-HG) was observed in IDH2-R172S, but not in IDH2-H175Y or IDH2-WT.

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).


Isocitrate dehydrogenase mutation is frequently observed in giant cell tumor of bone.

Kato Kaneko M, Liu X, Oki H, Ogasawara S, Nakamura T, Saidoh N, Tsujimoto Y, Matsuyama Y, Uruno A, Sugawara M, Tsuchiya T, Yamakawa M, Yamamoto M, Takagi M, Kato Y - Cancer Sci. (2014)

Isocitrate dehydrogenase 2 (IDH2)-H175Y (CAT > TAT) mutations were not detected by MsMab-1, a multispecific anti-IDH1/2 mAb. (a) DNA direct sequencing was carried out against bone sample no. 19. (b) Total cell lysate from U-2 OS osteosarcoma cells expressing IDH2 wild-type-PA tag (WT, lane 1) and IDH2 mutants (lane 2, IDH2-R172S-PA tag; lane 3, IDH2-H175Y-PA tag) were electrophoresed, and Western blotted using MsMab-1 or anti-PA tag (NZ-1). Production of oncometabolite R(-)-2-hydroxyglutarate (2-HG) was observed in IDH2-R172S, but not in IDH2-H175Y or IDH2-WT.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig03: Isocitrate dehydrogenase 2 (IDH2)-H175Y (CAT > TAT) mutations were not detected by MsMab-1, a multispecific anti-IDH1/2 mAb. (a) DNA direct sequencing was carried out against bone sample no. 19. (b) Total cell lysate from U-2 OS osteosarcoma cells expressing IDH2 wild-type-PA tag (WT, lane 1) and IDH2 mutants (lane 2, IDH2-R172S-PA tag; lane 3, IDH2-H175Y-PA tag) were electrophoresed, and Western blotted using MsMab-1 or anti-PA tag (NZ-1). Production of oncometabolite R(-)-2-hydroxyglutarate (2-HG) was observed in IDH2-R172S, but not in IDH2-H175Y or IDH2-WT.
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).

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%).

View Article: PubMed Central - PubMed

Affiliation: Department of Regional Innovation, Tohoku University Graduate School of Medicine, Sendai, Japan.

Show MeSH
Related in: MedlinePlus