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

M. Fernanda Amary; Stephen Damato; Dina Halai; Malihe Eskandarpour; Fitim Berisha; Fiona Bonar; Stan McCarthy; Valeria R. Fantin; Kimberly S. Straley; Samira Lobo; Will Aston; Claire L. Green; Rosemary E. Gale; Roberto Tirabosco; Andrew Futreal; Peter Campbell; Nadège Presneau; Adrienne M. Flanagan

doi:10.1038/ng.994

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

M. Fernanda Amary, Stephen Damato, Dina Halai, Malihe Eskandarpour, Fitim Berisha, Fiona Bonar, Stan McCarthy, Valeria R. Fantin, Kimberly S. Straley, Samira Lobo, Will Aston, Claire L. Green, Rosemary E. Gale, Roberto Tirabosco, Andrew Futreal, Peter Campbell, Nadège Presneau, Adrienne M. Flanagan^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

351 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1262-1265
Number of pages	4
Journal	Nature Genetics
Volume	43
Issue number	12
DOIs	https://doi.org/10.1038/ng.994
Publication status	Published - Dec 2011
Externally published	Yes

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Amary, M. F., Damato, S., Halai, D., Eskandarpour, M., Berisha, F., Bonar, F., McCarthy, S., Fantin, V. R., Straley, K. S., Lobo, S., Aston, W., Green, C. L., Gale, R. E., Tirabosco, R., Futreal, A., Campbell, P., Presneau, N., & Flanagan, A. M. (2011). Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2. Nature Genetics, 43(12), 1262-1265. https://doi.org/10.1038/ng.994

@article{999882ba1cfc46d9ae36e6cb788ae7f4,

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.",

author = "Amary, {M. Fernanda} and Stephen Damato and Dina Halai and Malihe Eskandarpour and Fitim Berisha and Fiona Bonar and Stan McCarthy and Fantin, {Valeria R.} and Straley, {Kimberly S.} and Samira Lobo and Will Aston and Green, {Claire L.} and Gale, {Rosemary E.} and Roberto Tirabosco and Andrew Futreal and Peter Campbell and Nad{\`e}ge Presneau and Flanagan, {Adrienne M.}",

year = "2011",

month = dec,

doi = "10.1038/ng.994",

language = "English",

volume = "43",

pages = "1262--1265",

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Amary, MF, Damato, S, Halai, D, Eskandarpour, M, Berisha, F, Bonar, F, McCarthy, S, Fantin, VR, Straley, KS, Lobo, S, Aston, W, Green, CL, Gale, RE, Tirabosco, R, Futreal, A, Campbell, P, Presneau, N & Flanagan, AM 2011, 'Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2', Nature Genetics, vol. 43, no. 12, pp. 1262-1265. https://doi.org/10.1038/ng.994

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AU - Amary, M. Fernanda

AU - Damato, Stephen

AU - Halai, Dina

AU - Eskandarpour, Malihe

AU - Berisha, Fitim

AU - Bonar, Fiona

AU - McCarthy, Stan

AU - Fantin, Valeria R.

AU - Straley, Kimberly S.

AU - Lobo, Samira

AU - Aston, Will

AU - Green, Claire L.

AU - Gale, Rosemary E.

AU - Tirabosco, Roberto

AU - Futreal, Andrew

AU - Campbell, Peter

AU - Presneau, Nadège

AU - Flanagan, Adrienne M.

PY - 2011/12

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AB - 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.

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JO - Nature Genetics

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

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