Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2

• Published in: Nature genetics Vol. 43; no. 12; pp. 1262 - 1265
• Main Authors: Amary, M Fernanda, Damato, Stephen, Halai, Dina, Eskandarpour, Malihe, Berisha, Fitim, Bonar, Fiona, McCarthy, Stan, Fantin, Valeria R, Straley, Kimberly S, Lobo, Samira, Aston, Will, Green, Claire L, Gale, Rosemary E, Tirabosco, Roberto, Futreal, Andrew, Campbell, Peter, Presneau, Nadège, Flanagan, Adrienne M
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2011; Nature Publishing Group
• Subjects: 631/208/737; 692/420; 692/699/67/1344; Adolescent; Adult; Aged; Aged, 80 and over; Agriculture; Angioma; Animal Genetics and Genomics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Bone diseases; Cancer Research; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Child; Colleges & universities; Diseases of the osteoarticular system; Dysplasia; Enchondromatosis - genetics; Female; Fundamental and applied biological sciences. Psychology; Gene Function; Gene mutations; Genetic aspects; Genetic Association Studies; Genetics of eukaryotes. Biological and molecular evolution; Health aspects; Human Genetics; Humans; Isocitrate Dehydrogenase - genetics; letter; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical research; Medical sciences; Metabolites; Middle Aged; Molecular and cellular biology; Mosaicism; Mutation; Mutation, Missense; Risk factors; Sequence Analysis, DNA; Tumors; Young Adult; United States; United Kingdom; Vascular disease; Somatic mutation; Skin disease; Angioma; Syndrome de Maffucci; Diseases of the osteoarticular system; Cardiovascular disease; Tumor; Congenital disease; Osteochondrodysplasia
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.994

Adrienne Flanagan and colleagues report the identification of somatic mosaic mutations in the IDH1 and IDH2 genes in tumors from individuals with Ollier disease and Maffucci syndrome, diseases that are characterized by the presence of multiple central cartilaginous tumors that are accompanied by soft tissue hemangiomas in Maffucci syndrome. 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.