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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

335 Citations (Scopus)


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
Issue number1
Publication statusPublished - Jan 2009


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