Dataset Information

IDH mutations: genotype-phenotype correlation and prognostic impact.

ABSTRACT: IDH1/2 mutation is the most frequent genomic alteration found in gliomas, affecting 40% of these tumors and is one of the earliest alterations occurring in gliomagenesis. We investigated a series of 1305 gliomas and showed that IDH mutation is almost constant in 1p19q codeleted tumors. We found that the distribution of IDH1(R132H) , IDH1(nonR132H) , and IDH2 mutations differed between astrocytic, mixed, and oligodendroglial tumors, with an overrepresentation of IDH2 mutations in oligodendroglial phenotype and an overrepresentation of IDH1(nonR132H) in astrocytic tumors. We stratified grade II and grade III gliomas according to the codeletion of 1p19q and IDH mutation to define three distinct prognostic subgroups: 1p19q and IDH mutated, IDH mutated--which contains mostly TP53 mutated tumors, and none of these alterations. We confirmed that IDH mutation with a hazard ratio = 0.358 is an independent prognostic factor of good outcome. These data refine current knowledge on IDH mutation prognostic impact and genotype-phenotype associations.

SUBMITTER: Wang XW

PROVIDER: S-EPMC4022066 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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IDH mutations: genotype-phenotype correlation and prognostic impact.

Wang Xiao-Wei XW Ciccarino Pietro P Rossetto Marta M Boisselier Blandine B Marie Yannick Y Desestret Virginie V Gleize Vincent V Mokhtari Karima K Sanson Marc M Labussière Marianne M

BioMed research international 20140430

IDH1/2 mutation is the most frequent genomic alteration found in gliomas, affecting 40% of these tumors and is one of the earliest alterations occurring in gliomagenesis. We investigated a series of 1305 gliomas and showed that IDH mutation is almost constant in 1p19q codeleted tumors. We found that the distribution of IDH1(R132H) , IDH1(nonR132H) , and IDH2 mutations differed between astrocytic, mixed, and oligodendroglial tumors, with an overrepresentation of IDH2 mutations in oligodendroglial ...[more]

PMID: 24877111

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Project description:Holoprosencephaly (HPE), which results from failed or incomplete midline forebrain division early in gestation, is the most common forebrain malformation. The etiology of HPE is complex and multifactorial. To date, at least 12 HPE-associated genes have been identified, including TGIF (transforming growth factor beta-induced factor), located on chromosome 18p11.3. TGIF encodes a transcriptional repressor of retinoid responses involved in TGF-? signaling regulation, including Nodal signaling. TGIF mutations are reported in approximately 1-2% of patients with non-syndromic, non-chromosomal HPE. We combined data from our comprehensive studies of HPE with a literature search for all individuals with HPE and evidence of mutations affecting TGIF in order to establish the genotypic and phenotypic range. We describe 2 groups of patients: 34 with intragenic mutations and 21 with deletions of TGIF. These individuals, which were ascertained from our research group, in collaboration with other centers, and through a literature search, include 38 probands and 17 mutation-positive relatives. The majority of intragenic mutations occur in the TGIF homeodomain. Patients with mutations affecting TGIFrecapitulate the entire phenotypic spectrum observed in non-chromosomal, non-syndromic HPE. We identified a statistically significant difference between the 2 groups with respect to inheritance, as TGIF deletions were more likely to be de novo in comparison to TGIF mutations (?(2) ((2)) = 6.97, p(permutated) = 0.0356). In addition, patients with TGIF deletions were also found to more commonly present with manifestations beyond the craniofacial and neuroanatomical features associated with HPE (p = 0.0030). These findings highlight differences in patients with intragenic mutations versus deletions affecting TGIF, and draw attention to the homeodomain region, which appears to be particularly relevant to HPE. These results may be useful for genetic counseling of affected patients.

Dataset Information

IDH mutations: genotype-phenotype correlation and prognostic impact.

Publications

IDH mutations: genotype-phenotype correlation and prognostic impact.

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