J Pathol Transl Med.  2015 May;49(3):257-261. 10.4132/jptm.2015.04.14.

IDH Mutation Analysis in Ewing Sarcoma Family Tumors

• Na KY
• Noh BJ
• Sung JY
• Kim YW
• Santini Araujo E
• Park YK

• KMID: 2381385
• DOI: http://doi.org/10.4132/jptm.2015.04.14

Abstract

BACKGROUND
Isocitrate dehydrogenase (IDH) catalyzes the oxidative decarboxylation of isocitrate to yield alpha-ketoglutarate (alpha-KG) with production of reduced nicotinamide adenine dinucleotide (NADH). Dysfunctional IDH leads to reduced production of alpha-KG and NADH and increased production of 2-hydroxyglutarate, an oncometabolite. This results in increased oxidative damage and stabilization of hypoxia-inducible factor alpha, causing cells to be prone to tumorigenesis.
METHODS
This study investigated IDH mutations in 61 Ewing sarcoma family tumors (ESFTs), using a pentose nucleic acid clamping method and direct sequencing.
RESULTS
We identified four cases of ESFTs harboring IDH mutations. The number of IDH1 and IDH2 mutations was equal and the subtype of IDH mutations was variable. Clinicopathologic analysis according to IDH mutation status did not reveal significant results.
CONCLUSIONS
This study is the first to report IDH mutations in ESFTs. The results indicate that ESFTs can harbor IDH mutations in previously known hot-spot regions, although their incidence is rare. Further validation with a larger case-based study would establish more reliable and significant data on prevalence rate and the biological significance of IDH mutations in ESFTs.

Keyword

Isocitrate dehydrogenase; Sarcoma, Ewing; PNA clamping

MeSH Terms

Carcinogenesis
Constriction
Decarboxylation
Humans
Incidence
Isocitrate Dehydrogenase
NAD
Prevalence
Sarcoma, Ewing*
Isocitrate Dehydrogenase
NAD

Figure

• 

  Fig. 1. The case No. 1 sample shows IDH1 R132H mutation by direct sequencing (A) and positive immunoreactivity with antibody clone H09 (B). The case No. 4 sample shows IDH2 R172K mutation (C).

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