title: Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2.
abstract: Ollier disease and Maffucci syndrome are characterized by multiple central cartilaginous tumors that are accompanied by soft tissue hemangiomas in Maffucci syndrome. We show that in 37 of 40 individuals with these syndromes, at least one tumor has a mutation in isocitrate dehydrogenase 1 (IDH1) or in IDH2, 65% of which result in a R132C substitution in the protein. In 18 of 19 individuals with more than one tumor analyzed, all tumors from a given individual shared the same IDH1 mutation affecting Arg132. In 2 of 12 subjects, a low level of mutated DNA was identified in non-neoplastic tissue. The levels of the metabolite 2HG were measured in a series of central cartilaginous and vascular tumors, including samples from syndromic and nonsyndromic subjects, and these levels correlated strongly with the presence of IDH1 mutations. The findings are compatible with a model in which IDH1 or IDH2 mutations represent early post-zygotic occurrences in individuals with these syndromes.
authors: Histopathology Unit, Royal National Orthopaedic Hospital National Health Service Trust, Stanmore, UK. a.flanagan@ucl.ac.uk
authors: M Fernanda
authors: MF
authors: Amary
authors: Stephen
authors: S
authors: Damato
authors: Dina
authors: D
authors: Halai
authors: Malihe
authors: M
authors: Eskandarpour
authors: Fitim
authors: F
authors: Berisha
authors: Fiona
authors: F
authors: Bonar
authors: Stan
authors: S
authors: McCarthy
authors: Valeria R
authors: VR
authors: Fantin
authors: Kimberly S
authors: KS
authors: Straley
authors: Samira
authors: S
authors: Lobo
authors: Will
authors: W
authors: Aston
authors: Claire L
authors: CL
authors: Green
authors: Rosemary E
authors: RE
authors: Gale
authors: Roberto
authors: R
authors: Tirabosco
authors: Andrew
authors: A
authors: Futreal
authors: Peter
authors: P
authors: Campbell
authors: Nadège
authors: N
authors: Presneau
authors: Adrienne M
authors: AM
authors: Flanagan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D004687:Enchondromatosis / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009030:Mosaicism; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human