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IDH1 mutations at residue p.R132 ( IDH1 R132 ) occur frequently in high‐grade gliomas but not in other solid tumors
Author(s) -
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
Publication year - 2009
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20937
Subject(s) - isocitrate dehydrogenase , idh1 , idh2 , glioma , chemistry , cancer research , gene , microbiology and biotechnology , mutation , biology , enzyme , biochemistry
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 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. Hum Mutat 30, 7–11, 2009. © 2008 Wiley‐Liss, Inc.