IDH1 Mutations at Residue p.R132 (IDH1(R132)) 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 journalArticleAcademicpeer-review

342 Citations (Scopus)


Systematic sequence profiling of the Glio. blastoma 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 IDH1(R132) 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 IDH1(R132) in GBM. Strikingly, no IDH1 mutations were detected in the other tumor types. These data indicate that cancer mutations affecting IDH1(R132) 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
JournalHuman mutation
Issue number1
Publication statusPublished - 2009

Cite this