title: Isocitrate dehydrogenase 2 mutation is a frequent event in osteosarcoma detected by a multi-specific monoclonal antibody MsMab-1.
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.
authors.affiliation: Department of Regional Innovation, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan; Department of Orthopaedic Surgery, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.forename: Yukinari
authors.initials: Y
authors.lastname: Kato
authors.forename: Mika Kato
authors.initials: MK
authors.lastname: Kaneko
authors.forename: Masato
authors.initials: M
authors.lastname: Sugawara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogasawara
authors.forename: Yuta
authors.initials: Y
authors.lastname: Tsujimoto
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Naganuma
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Yamakawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: Michiaki
authors.initials: M
authors.lastname: Takagi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001859:Bone Neoplasms / Q000235:genetics*; D016466:CHO Cells; D045744:Cell Line, Tumor; D002648:Child; D003412:Cricetulus; D005260:Female; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D012516:Osteosarcoma / Q000235:genetics*; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: Isocitrate dehydrogenase 1; isocitrate dehydrogenase 2; monoclonal antibody; mutations; osteosarcoma