Characterisation of isocitrate dehydrogenase 1/isocitrate dehydrogenase 2 gene mutation and the d-2-hydroxyglutarate oncometabolite level in dedifferentiated chondrosarcoma.
IDH1
IDH2
2-hydroxyglutarate
IDH mutation
cartilaginous neoplasms
dedifferentiated chondrosarcoma
sarcoma
Journal
Histopathology
ISSN: 1365-2559
Titre abrégé: Histopathology
Pays: England
ID NLM: 7704136
Informations de publication
Date de publication:
Apr 2020
Apr 2020
Historique:
received:
06
08
2019
accepted:
11
10
2019
pubmed:
15
10
2019
medline:
27
2
2021
entrez:
15
10
2019
Statut:
ppublish
Résumé
Dedifferentiated chondrosarcoma (DDCHS) is an aggressive type of chondrosarcoma that results from high-grade transformation of a low-grade chondrosarcoma. Mutations in the isocitrate dehydrogenase (IDH) 1 gene and the IDH2 gene that lead to increased d-2-hydroxyglutarate (2HG) oncometabolite production, promoting tumorigenesis, have been recently described in low-grade cartilaginous neoplasms. The aims of this study were to examine the prevalence of IDH mutations in a single-institution cohort of DDCHS cases and correlate 2HG levels with mutation status. We examined a series of 21 primary DDCHS cases by using Sanger sequencing and quantitative polymerase chain reaction genotyping to look for IDH1/IDH2 mutations, and evaluated the 2HG levels in formalin-fixed paraffin-embedded tumour and matched normal tissue samples by using a fluorometric assay. Seventy-six per cent of DDCHS cases (16/21) harboured a heterozygous IDH1 or IDH2 mutation. Six of 14 IDH-mutated DDCHS cases showed elevated 2HG levels in tumour tissue relative to matched normal tissue. There were no consistent histological or disease-specific survival differences between IDH-mutated tumours and wild-type tumours. 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. Similarly to other IDH-mutated tumour types, IDH-mutated DDCHS cases show elevated 2HG levels, indicating that the oncometabolite activity of 2HG may contribute to DDCHS oncogenesis and progression.
Substances chimiques
Glutarates
0
alpha-hydroxyglutarate
2889-31-8
IDH2 protein, human
EC 1.1.1.41
Isocitrate Dehydrogenase
EC 1.1.1.41
IDH1 protein, human
EC 1.1.1.42.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
722-730Subventions
Organisme : BC Cancer Foundation
Organisme : BC Cancer
Organisme : Vancouver Coastal Health Research Institute
Informations de copyright
© 2019 John Wiley & Sons Ltd.
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