Isocitrate dehydrogenase 2 mutation is a frequent event in osteosarcoma detected by a multi‐specific monoclonal antibody MsMab‐1

Cancer Medicine

Xing Liu¹  Yukinari Kato¹  Mika Kato Kaneko¹  Masato Sugawara²  Satoshi Ogasawara¹  Yuta Tsujimoto¹  Yasushi Naganuma²  Mitsunori Yamakawa³  Takashi Tsuchiya² 

[1] Department of Regional Innovation, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan;Department of Orthopaedic Surgery, Yamagata University School of Medicine, Yamagata, Japan;Department of Diagnostic Pathology, Yamagata University School of Medicine, Yamagata, Japan

关键词: Isocitrate dehydrogenase 1;    isocitrate dehydrogenase 2;    monoclonal antibody;    mutations;    osteosarcoma;   

DOI  :  10.1002/cam4.149

来源: Wiley

【 摘 要 】

Abstract

Somatic mutations of isocitrate dehydrogenase (IDH) 1 and IDH2 occur in gliomas, acute myeloid leukemia, and cartilaginous tumors. Somatic mosaic IDH1/2 mutations are also reported in Ollier disease and Maffucci syndrome, which are characterized by multiple central cartilaginous tumors. Although IDH1/2 mutation analysis against osteosarcoma has been performed in several studies, no IDH1/2 mutation has been reported. Herein, we newly report the IDH2-R172S mutation in three of 12 (25%) osteosarcoma patients, which was detected by direct DNA sequencing. No monoclonal antibody (mAb) has been reported against IDH2-R172S mutation. However, we demonstrate that the IDH2-R172S peptide was recognized by our established multi-specific anti-mutated IDH1/2 mAb, MsMab-1, in enzyme-linked immunosorbent assay. Western blot analysis revealed that MsMab-1 reacts with PA tag combined recombinant proteins of IDH2-R172S. Furthermore, MsMab-1 stained IDH2-R172S-expressing osteosarcoma tissues in immunohistochemistry. The MsMab-1 stained nine of 32 (28.1%) osteosarcomas in a tissue microarray. This report is the first describing IDH2 mutations in osteosarcoma, which can be detected by MsMab-1 mAb. Taken together, these results show that MsMab-1 can be anticipated for use in immunohistochemical determination of IDH1/2 mutation-bearing osteosarcoma.

【 授权许可】

CC BY   
© 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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