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IDH Mutation Analysis in Ewing Sarcoma Family Tumors.

Na KY, Noh BJ, Sung JY, Kim YW, Santini Araujo E, Park YK - J Pathol Transl Med (2015)

Bottom Line: Clinicopathologic analysis according to IDH mutation status did not reveal significant results.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Central Physical Examination Agency, Daegu, Korea.

ABSTRACT

Background: Isocitrate dehydrogenase (IDH) catalyzes the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG) with production of reduced nicotinamide adenine dinucleotide (NADH). Dysfunctional IDH leads to reduced production of α-KG and NADH and increased production of 2-hydroxyglutarate, an oncometabolite. This results in increased oxidative damage and stabilization of hypoxia-inducible factor α, 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.

No MeSH data available.


Related in: MedlinePlus

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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f1-jptm-49-3-257: 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).

Mentions: Table 2 summarizes the clinicopathologic characteristics of the four mutant cases. In one of four cases, the IDH1 mutation was found by both the PNA clamping method and direct sequencing (case No. 1) (Fig. 1A). In two of four cases, the IDH1/2 mutation was found only by the PNA clamping method (cases Nos. 2 and 3). In one of four cases, examination by the PNA clamping method showed equivocal results, but direct sequencing showed an IDH2 mutation (case No. 4) (Fig. 1C). The overall concordance rate of both methods was over 95% (58 of 61) and the discordance rate was less than 5% (3 of 61). In mutant cases, the concordance rate was 25% (1 of 4) and the discordance rate was 75% (3 of 4), although case No. 4 showed equivocal results by the PNA clamping method. Immunohistochemistry with antibody to DIA-H09 in the four cases bearing IDH1/2 mutations showed positive reactions only in case No. 1 (Fig. 1B).


IDH Mutation Analysis in Ewing Sarcoma Family Tumors.

Na KY, Noh BJ, Sung JY, Kim YW, Santini Araujo E, Park YK - J Pathol Transl Med (2015)

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).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4440938&req=5

f1-jptm-49-3-257: 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).
Mentions: Table 2 summarizes the clinicopathologic characteristics of the four mutant cases. In one of four cases, the IDH1 mutation was found by both the PNA clamping method and direct sequencing (case No. 1) (Fig. 1A). In two of four cases, the IDH1/2 mutation was found only by the PNA clamping method (cases Nos. 2 and 3). In one of four cases, examination by the PNA clamping method showed equivocal results, but direct sequencing showed an IDH2 mutation (case No. 4) (Fig. 1C). The overall concordance rate of both methods was over 95% (58 of 61) and the discordance rate was less than 5% (3 of 61). In mutant cases, the concordance rate was 25% (1 of 4) and the discordance rate was 75% (3 of 4), although case No. 4 showed equivocal results by the PNA clamping method. Immunohistochemistry with antibody to DIA-H09 in the four cases bearing IDH1/2 mutations showed positive reactions only in case No. 1 (Fig. 1B).

Bottom Line: Clinicopathologic analysis according to IDH mutation status did not reveal significant results.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Central Physical Examination Agency, Daegu, Korea.

ABSTRACT

Background: Isocitrate dehydrogenase (IDH) catalyzes the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG) with production of reduced nicotinamide adenine dinucleotide (NADH). Dysfunctional IDH leads to reduced production of α-KG and NADH and increased production of 2-hydroxyglutarate, an oncometabolite. This results in increased oxidative damage and stabilization of hypoxia-inducible factor α, 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.

No MeSH data available.


Related in: MedlinePlus