IDH1 mutations at residue p.R132 (IDH1R132) occur frequently in high-grade gliomas but not in other solid tumors

Fonnet E. Bleeker, Simona Lamba, Sieger Leenstra, Dirk Troost, Theo Hulsebos, W. Peter Vandertop, Milo Frattini, Francesca Molinari, Margaret Knowles, Aniello Cerrato, Monica Rodolfo, Aldo Scarpa, Lara Felicioni, Fiamma Buttitta, Sara Malatesta, Antonio Marchetti, Alberto Bardelli

Research output: Contribution to journalArticle

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Abstract

Systematic sequence profiling of the Glioblastoma Multiforme (GBM) genome has recently led to the identification of somatic mutations in the isocitrate dehydrogenase 1 (IDH1) gene. Interestingly, only the evolutionarily conserved residue R132 located in the substrate binding site of IDH1 was found mutated in GBM. At present, the occurrence and the relevance of p.R132 (IDH1 R132) variants in tumors other than GBMs is largely unknown. We searched for mutations at position R132 of the IDH1 gene in a panel of 672 tumor samples. These included high-grade glioma, gastrointestinal stromal tumors (GIST), melanoma, bladder, breast, colorectal, lung, ovarian, pancreas, prostate, and thyroid carcinoma specimens. In addition, we assessed a panel of 84 cell lines from different tumor lineages. Somatic mutations affecting the IDH1R132 residue were detected in 20% (23 of 113) high-grade glioma samples. In addition to the previously reported p.R132H and p.R132S alleles, we identified three novel somatic mutations (p.R132C, p.R132G, and p.R132L) affecting residue IDH1R132 in GBM. Strikingly, no IDH1 mutations were detected in the other tumor types. These data indicate that cancer mutations affecting IDH1R132 are tissue-specific, and suggest that it plays a unique role in the development of high-grade gliomas.

Original languageEnglish
Pages (from-to)7-11
Number of pages5
JournalHuman Mutation
Volume30
Issue number1
DOIs
Publication statusPublished - Jan 2009

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Isocitrate Dehydrogenase
Glioma
Mutation
Glioblastoma
Neoplasms
Gastrointestinal Stromal Tumors
Tumor Cell Line
Thyroid Neoplasms
Genes
Prostate
Pancreas
Melanoma
Urinary Bladder
Breast
Alleles
Binding Sites
Genome
Lung

Keywords

  • Cancer
  • GBM
  • HGG
  • IDH1
  • Somatic mutation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

IDH1 mutations at residue p.R132 (IDH1R132) occur frequently in high-grade gliomas but not in other solid tumors. / Bleeker, Fonnet E.; Lamba, Simona; Leenstra, Sieger; Troost, Dirk; Hulsebos, Theo; Vandertop, W. Peter; Frattini, Milo; Molinari, Francesca; Knowles, Margaret; Cerrato, Aniello; Rodolfo, Monica; Scarpa, Aldo; Felicioni, Lara; Buttitta, Fiamma; Malatesta, Sara; Marchetti, Antonio; Bardelli, Alberto.

In: Human Mutation, Vol. 30, No. 1, 01.2009, p. 7-11.

Research output: Contribution to journalArticle

Bleeker, FE, Lamba, S, Leenstra, S, Troost, D, Hulsebos, T, Vandertop, WP, Frattini, M, Molinari, F, Knowles, M, Cerrato, A, Rodolfo, M, Scarpa, A, Felicioni, L, Buttitta, F, Malatesta, S, Marchetti, A & Bardelli, A 2009, 'IDH1 mutations at residue p.R132 (IDH1R132) occur frequently in high-grade gliomas but not in other solid tumors', Human Mutation, vol. 30, no. 1, pp. 7-11. https://doi.org/10.1002/humu.20937
Bleeker, Fonnet E. ; Lamba, Simona ; Leenstra, Sieger ; Troost, Dirk ; Hulsebos, Theo ; Vandertop, W. Peter ; Frattini, Milo ; Molinari, Francesca ; Knowles, Margaret ; Cerrato, Aniello ; Rodolfo, Monica ; Scarpa, Aldo ; Felicioni, Lara ; Buttitta, Fiamma ; Malatesta, Sara ; Marchetti, Antonio ; Bardelli, Alberto. / IDH1 mutations at residue p.R132 (IDH1R132) occur frequently in high-grade gliomas but not in other solid tumors. In: Human Mutation. 2009 ; Vol. 30, No. 1. pp. 7-11.
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abstract = "Systematic sequence profiling of the Glioblastoma Multiforme (GBM) genome has recently led to the identification of somatic mutations in the isocitrate dehydrogenase 1 (IDH1) gene. Interestingly, only the evolutionarily conserved residue R132 located in the substrate binding site of IDH1 was found mutated in GBM. At present, the occurrence and the relevance of p.R132 (IDH1 R132) variants in tumors other than GBMs is largely unknown. We searched for mutations at position R132 of the IDH1 gene in a panel of 672 tumor samples. These included high-grade glioma, gastrointestinal stromal tumors (GIST), melanoma, bladder, breast, colorectal, lung, ovarian, pancreas, prostate, and thyroid carcinoma specimens. In addition, we assessed a panel of 84 cell lines from different tumor lineages. Somatic mutations affecting the IDH1R132 residue were detected in 20{\%} (23 of 113) high-grade glioma samples. In addition to the previously reported p.R132H and p.R132S alleles, we identified three novel somatic mutations (p.R132C, p.R132G, and p.R132L) affecting residue IDH1R132 in GBM. Strikingly, no IDH1 mutations were detected in the other tumor types. These data indicate that cancer mutations affecting IDH1R132 are tissue-specific, and suggest that it plays a unique role in the development of high-grade gliomas.",
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AU - Bleeker, Fonnet E.

AU - Lamba, Simona

AU - Leenstra, Sieger

AU - Troost, Dirk

AU - Hulsebos, Theo

AU - Vandertop, W. Peter

AU - Frattini, Milo

AU - Molinari, Francesca

AU - Knowles, Margaret

AU - Cerrato, Aniello

AU - Rodolfo, Monica

AU - Scarpa, Aldo

AU - Felicioni, Lara

AU - Buttitta, Fiamma

AU - Malatesta, Sara

AU - Marchetti, Antonio

AU - Bardelli, Alberto

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N2 - Systematic sequence profiling of the Glioblastoma Multiforme (GBM) genome has recently led to the identification of somatic mutations in the isocitrate dehydrogenase 1 (IDH1) gene. Interestingly, only the evolutionarily conserved residue R132 located in the substrate binding site of IDH1 was found mutated in GBM. At present, the occurrence and the relevance of p.R132 (IDH1 R132) variants in tumors other than GBMs is largely unknown. We searched for mutations at position R132 of the IDH1 gene in a panel of 672 tumor samples. These included high-grade glioma, gastrointestinal stromal tumors (GIST), melanoma, bladder, breast, colorectal, lung, ovarian, pancreas, prostate, and thyroid carcinoma specimens. In addition, we assessed a panel of 84 cell lines from different tumor lineages. Somatic mutations affecting the IDH1R132 residue were detected in 20% (23 of 113) high-grade glioma samples. In addition to the previously reported p.R132H and p.R132S alleles, we identified three novel somatic mutations (p.R132C, p.R132G, and p.R132L) affecting residue IDH1R132 in GBM. Strikingly, no IDH1 mutations were detected in the other tumor types. These data indicate that cancer mutations affecting IDH1R132 are tissue-specific, and suggest that it plays a unique role in the development of high-grade gliomas.

AB - Systematic sequence profiling of the Glioblastoma Multiforme (GBM) genome has recently led to the identification of somatic mutations in the isocitrate dehydrogenase 1 (IDH1) gene. Interestingly, only the evolutionarily conserved residue R132 located in the substrate binding site of IDH1 was found mutated in GBM. At present, the occurrence and the relevance of p.R132 (IDH1 R132) variants in tumors other than GBMs is largely unknown. We searched for mutations at position R132 of the IDH1 gene in a panel of 672 tumor samples. These included high-grade glioma, gastrointestinal stromal tumors (GIST), melanoma, bladder, breast, colorectal, lung, ovarian, pancreas, prostate, and thyroid carcinoma specimens. In addition, we assessed a panel of 84 cell lines from different tumor lineages. Somatic mutations affecting the IDH1R132 residue were detected in 20% (23 of 113) high-grade glioma samples. In addition to the previously reported p.R132H and p.R132S alleles, we identified three novel somatic mutations (p.R132C, p.R132G, and p.R132L) affecting residue IDH1R132 in GBM. Strikingly, no IDH1 mutations were detected in the other tumor types. These data indicate that cancer mutations affecting IDH1R132 are tissue-specific, and suggest that it plays a unique role in the development of high-grade gliomas.

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KW - HGG

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