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Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome

Pansuriya, Twinkal C.; van Eijk, Ronald; d'Adamo, Pio; van Ruler, Maayke A. J. H.; Kuijjer, Marieke L.; Oosting, Jan; Cleton-Jansen, Anne-Marie; van Oosterwijk, Jolieke G.; Verbeke, Sofie L. J. and Meijer, Danielle, et al. (2011) In Nature Genetics 43(12). p.1256-1261
Abstract
Ollier disease and Maffucci syndrome are non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease) combined with spindle cell hemangiomas (Maffucci syndrome). We report somatic heterozygous mutations in IDH1 (c.394C>T encoding an R132C substitution and c.395G>A encoding an R132H substitution) or IDH2 (c.516G>C encoding R172S) in 87% of enchondromas (benign cartilage tumors) and in 70% of spindle cell hemangiomas (benign vascular lesions). In total, 35 of 43 (81%) subjects with Ollier disease and 10 of 13 (77%) with Maffucci syndrome carried IDH1 (98%) or IDH2 (2%) mutations in their tumors. Fourteen of 16 subjects had identical mutations in separate lesions. Immunohistochemistry to detect mutant... (More)
Ollier disease and Maffucci syndrome are non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease) combined with spindle cell hemangiomas (Maffucci syndrome). We report somatic heterozygous mutations in IDH1 (c.394C>T encoding an R132C substitution and c.395G>A encoding an R132H substitution) or IDH2 (c.516G>C encoding R172S) in 87% of enchondromas (benign cartilage tumors) and in 70% of spindle cell hemangiomas (benign vascular lesions). In total, 35 of 43 (81%) subjects with Ollier disease and 10 of 13 (77%) with Maffucci syndrome carried IDH1 (98%) or IDH2 (2%) mutations in their tumors. Fourteen of 16 subjects had identical mutations in separate lesions. Immunohistochemistry to detect mutant IDH1 R132H protein suggested intraneoplastic and somatic mosaicism. IDH1 mutations in cartilage tumors were associated with hypermethylation and downregulated expression of several genes. Mutations were also found in 40% of solitary central cartilaginous tumors and in four chondrosarcoma cell lines, which will enable functional studies to assess the role of IDH1 and IDH2 mutations in tumor formation. (Less)
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@article{30da8101-5ac4-4585-865c-ff6ffdc81a0b,
  abstract     = {Ollier disease and Maffucci syndrome are non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease) combined with spindle cell hemangiomas (Maffucci syndrome). We report somatic heterozygous mutations in IDH1 (c.394C>T encoding an R132C substitution and c.395G>A encoding an R132H substitution) or IDH2 (c.516G>C encoding R172S) in 87% of enchondromas (benign cartilage tumors) and in 70% of spindle cell hemangiomas (benign vascular lesions). In total, 35 of 43 (81%) subjects with Ollier disease and 10 of 13 (77%) with Maffucci syndrome carried IDH1 (98%) or IDH2 (2%) mutations in their tumors. Fourteen of 16 subjects had identical mutations in separate lesions. Immunohistochemistry to detect mutant IDH1 R132H protein suggested intraneoplastic and somatic mosaicism. IDH1 mutations in cartilage tumors were associated with hypermethylation and downregulated expression of several genes. Mutations were also found in 40% of solitary central cartilaginous tumors and in four chondrosarcoma cell lines, which will enable functional studies to assess the role of IDH1 and IDH2 mutations in tumor formation.},
  author       = {Pansuriya, Twinkal C. and van Eijk, Ronald and d'Adamo, Pio and van Ruler, Maayke A. J. H. and Kuijjer, Marieke L. and Oosting, Jan and Cleton-Jansen, Anne-Marie and van Oosterwijk, Jolieke G. and Verbeke, Sofie L. J. and Meijer, Danielle and van Wezel, Tom and Hansén Nord, Karolin and Sangiorgi, Luca and Toker, Berkin and Liegl-Atzwanger, Bernadette and San-Julian, Mikel and Sciot, Raf and Limaye, Nisha and Kindblom, Lars-Gunnar and Daugaard, Soeren and Godfraind, Catherine and Boon, Laurence M. and Vikkula, Miikka and Kurek, Kyle C. and Szuhai, Karoly and French, Pim J. and Bovee, Judith V. M. G.},
  issn         = {1546-1718},
  language     = {eng},
  number       = {12},
  pages        = {1256--1261},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome},
  url          = {http://dx.doi.org/10.1038/ng.1004},
  volume       = {43},
  year         = {2011},
}