Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome
| Autor: | Luca Sangiorgi, Ronald van Eijk, Catherine Godfraind, Judith V.M.G. Bovée, Jolieke G. van Oosterwijk, Sofie L. J. Verbeke, Maayke A. J. H. van Ruler, Pio D'Adamo, Danielle Meijer, Bernadette Liegl-Atzwanger, Karolin Hansén Nord, Lars-Gunnar Kindblom, Raf Sciot, Kyle C. Kurek, Miikka Vikkula, Mikel San-Julian, Anne-Marie Cleton-Jansen, Jan Oosting, Nisha Limaye, Laurence M. Boon, Karoly Szuhai, Tom van Wezel, Berkin Toker, Soeren Daugaard, Marieke L. Kuijjer, Twinkal C. Pansuriya, Pim J. French |
|---|---|
| Přispěvatelé: | Virology, Molecular Genetics, Neurology, T. C., Pansuriya, R. v., Eijk, D'Adamo, ADAMO PIO, M. a., J, M. L., Kuijjer, J., Oosting, A., Cleton Jansen, J. G., Van, S. L., J, D., Meijer, T. v., Wezel, K. H., Nord, L., Sangiorgi, B., Toker, B., Liegl Atzwanger, M., San Julian, R., Sciot, N., Limaye, L., Kindblom, S., Daugaard, C., Godfraind, L. M., Boon, M., Vikkula, K. C., Kurek, K., Szuhai, P. J., French, J. V., M. |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male medicine.medical_specialty Pathology Transcription Genetic Mutation Missense Biology IDH2 Ollier disease Article IDH1 protein human Young Adult 03 medical and health sciences Isocitrate dehydrogenase 2 human 0302 clinical medicine Cell Line Tumor Internal medicine Genetics medicine Enchondroma Enchondromatosis Humans Enchondromatosis/genetics 030304 developmental biology 0303 health sciences Mosaicism Gene Expression Profiling Sequence Analysis DNA DNA Methylation Middle Aged medicine.disease Osteochondrodysplasia Isocitrate Dehydrogenase 3. Good health Maffucci syndrome Endocrinology Gene Expression Regulation Case-Control Studies 030220 oncology & carcinogenesis Female Human medicine Chondrosarcoma Genome-Wide Association Study Chondroma |
| Zdroj: | Nature Genetics, 43(12), 1256-U124. Nature Publishing Group Nature genetics Dadun. Depósito Académico Digital de la Universidad de Navarra instname Nature Genetics, 43(12), 1256-U124 |
| ISSN: | 1061-4036 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|