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6197988 
Journal Article 
Characterization of IDH1/IDH2 Mutation and D-2-Hydroxyglutarate Oncometabolite Level in Dedifferentiated Chondrosarcoma 
Mohammad, N; Wong, D; Lum, A; Lin, J; Ho, J; Lee, CH; Yip, S 
2019 
Yes 
Histopathology
ISSN: 0309-0167
EISSN: 1365-2559 
76 
5 
722-730 
English 
31609487 
WOS:000526957800010 
INTRODUCTION: Dedifferentiated chondrosarcoma (DDCHS) is an aggressive type of chondrosarcoma that results from high-grade transformation of a low-grade chondrosarcoma. Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations have been recently described in low-grade cartilaginous neoplasms which lead to increased D-2-hydroxyglutarate (2HG) oncometabolite production, promoting tumorigenesis.

AIMS: To examine the prevalence of IDH mutations in a single institution cohort of DDCHS and correlate 2HG levels to mutation status.

METHODS AND RESULTS: We examined a series of 21 primary DDCHS using Sanger sequencing and qPCR genotyping to interrogate for IDH1/2 mutations, and evaluated the level of 2HG in formalin-fixed paraffin-embedded (FFPE) tumor and matched normal tissue samples using a fluorometric assay. 76% of DDCHS (16/21) harbored a heterozygous IDH1 or IDH2 mutation. 6/14 IDH-mutated DDCHS showed elevated 2HG in tumor relative to matched normal tissue. There were no consistent histologic or disease specific survival differences between IDH-mutated tumors and wild-type tumors.

CONCLUSIONS: Our study confirms the frequent presence of a variety of IDH1 and IDH2 mutation variants, indicating that a sequencing-based approach is required for DDCHS if IDH is to be used as a diagnostic marker. Similar to other IDH-mutated tumor types, IDH-mutated DDCHS also show elevated 2HG level, indicating that the oncometabolite activity of 2HG may contribute to DDCHS oncogenesis and progression.