A single-tube, sensitive multiplex method for screening of isocitrate dehydrogenase 1 (IDH1) mutations

Chou, Wen‐Chien; Huang, Yen-Ning; Huang, Chih‐Fen; Tseng, Mei‐Hsuan; Tien, Hwei‐Fang

doi:10.1182/blood-2010-04-280636

Cited by 12 publications

(9 citation statements)

References 9 publications

(26 reference statements)

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“…Moreover, IDH2 mutation was an independent favorable prognostic factor in multivariate analysis. Finally, by a comprehensive sequential study, we confirmed that IDH2 mutation, like IDH1 mutation we previously described, 14,19 was a stable mutation during disease evolution.…”

Section: Introductionsupporting

confidence: 63%

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The prognostic impact and stability of Isocitrate dehydrogenase 2 mutation in adult patients with acute myeloid leukemia

et al. 2010

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Although the clinical features of the Isocitrate dehydrogenase 2 (IDH2) mutation in acute myeloid leukemia (AML) have been characterized, its prognostic significance remains controversial and its stability has not been investigated. We analyzed 446 adults with primary non-M3 AML and found IDH2 R172, R140 and IDH1 R132 mutations occurred at a frequency of 2.9, 9.2 and 6.1%, respectively. Compared with wild-type IDH2, mutation of IDH2 was associated with higher platelet counts, intermediate-risk or normal karyotype and isolated þ 8, but was inversely correlated with expression of HLA-DR, CD34, CD15, CD7 and CD56, and was mutually exclusive with WT1 mutation and chromosomal translocations involving core-binding factors. All these correlations became stronger when IDH1 and IDH2 mutations were considered together. Multivariate analysis revealed IDH2 mutation as an independent favorable prognostic factor. IDH2 À /FLT3-ITD þ genotype conferred especially negative impact on survival. Compared with IDH2 R140 mutation, IDH2 R172 mutation was associated with younger age, lower white blood cell count and lactate dehydrogenase level, and was mutually exclusive with NPM1 mutation. Serial analyses of IDH2 mutations at both diagnosis and relapse in 121 patients confirmed high stability of IDH2 mutations. In conclusion, IDH2 mutation is a stable marker during disease evolution and confers favorable prognosis.

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Section: Introductionsupporting

confidence: 63%

“…This is the first report of sequential study of IDH2 mutation at both diagnosis and relapse in AML patients throughout the clinical course. We found that, like IDH1 mutation, 14,19 IDH2 mutation seemed quite stable.…”

Section: Discussionmentioning

confidence: 81%

The prognostic impact and stability of Isocitrate dehydrogenase 2 mutation in adult patients with acute myeloid leukemia

et al. 2010

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“…When a SNaPshot assay was used to track IDH mutation status of three patients, the only patient with detectable R132H IDH1 mutations in the bone marrow after induction chemotherapy was also the only one of these patients to relapse (69). One study used a high-sensitivity multiplex PCR method to screen for R132 IDH1 mutations by creating a pool of mutation-specific primers that generate PCR products of different lengths in mutant versus wildtype samples (70). Another approach is to utilize PCR-denaturing high performance liquid chromatography (PCR-DHPLC) to detect heterozygous mutation before further examination with Sanger sequencing (58).…”

Section: Detecting Idh Mutation In Clinical Specimensmentioning

confidence: 99%

Isocitrate dehydrogenase mutations in leukemia

McKenney

Levine²

2013

J. Clin. Invest.

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Recent genome-wide discovery studies have identified a spectrum of mutations in different malignancies and have led to the elucidation of novel pathways that contribute to oncogenic transformation. The discovery of mutations in the genes encoding isocitrate dehydrogenase (IDH) has uncovered a critical role for altered metabolism in oncogenesis, and the neomorphic, oncogenic function of IDH mutations affects several epigenetic and gene regulatory pathways. Here we discuss the relevance of IDH mutations to leukemia pathogenesis, therapy, and outcome and how mutations in IDH1 and IDH2 affect the leukemia epigenome, hematopoietic differentiation, and clinical outcome. IntroductionMutations in isocitrate dehydrogenase (IDH) have been identified in a spectrum of human malignancies. Mutations in IDH1 were first identified in an exome resequencing analysis of patients with colorectal cancer (1). Shortly thereafter, recurrent IDH1 and IDH2 mutations were found in patients with glioma, most commonly in patients who present with lower-grade gliomas (2). IDH1 mutations were subsequently discovered in patients with acute myeloid leukemia (AML) through whole genome sequencing (3), which was followed by the identification of somatic IDH2 mutations in patients with AML (4-6). Further studies revealed that IDH mutations induce a neomorphic function to produce the oncometabolite 2-hydroxyglutarate (2HG) (7,8), which can inhibit many cellular processes (9, 10). In particular, the ability of 2HG to alter the epigenetic landscape makes IDH a prototypical target for prognostic studies and drug targeting in leukemias.

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“…(Chou, et al 2010a, Chou, et al 2011c We have developed a single-tube, highly sensitive and specific PCR method to detect all IDH1 mutations at R132 residue. (Chou, et al 2010c) However, the IDH mutation is not a good marker for MRD monitoring because the minimal difference between the point mutation and normal allele. Other gene mutations are not readily applicable in MRD monitoring.…”

Section: Gene Mutations As Markers To Monitor Minimal Residual Diseasmentioning

confidence: 99%

Genetic Alterations and Their Clinical Implications in Acute Myeloid Leukemia

Hou¹,

Chou²,

Tien³

2011

Myeloid Leukemia - Basic Mechanisms of Leukemogenesis

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A single-tube, sensitive multiplex method for screening of isocitrate dehydrogenase 1 (IDH1) mutations

Cited by 12 publications

References 9 publications

The prognostic impact and stability of Isocitrate dehydrogenase 2 mutation in adult patients with acute myeloid leukemia

The prognostic impact and stability of Isocitrate dehydrogenase 2 mutation in adult patients with acute myeloid leukemia

Isocitrate dehydrogenase mutations in leukemia

Genetic Alterations and Their Clinical Implications in Acute Myeloid Leukemia

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