IDH1 immunohistochemistry reactivity and mosaic IDH1 or IDH2 somatic mutations in pediatric sporadic enchondroma and enchondromatosis

Article Article scientifique Article IDH1 immunohistochemistry reactivity and mosaic IDH1 or IDH2 somatic mutations in pediatric sporadic enchondroma and enchondromatosis eng 2019 author Saiji Essia 664737 author Gumy Pause Fabienne 0000-0002-2835-4367 133418 author Lascombes Pierre François Marie 779863 author Cerato Christelle 647642 author Marq-Lin Nathalie 24651 author Berczy Margaret 34818 author Merlini Laura 593185 author Rougemont-Pidoux Anne-Laure 29140 10.1007/s00428-019-02606-9 31240473 0945-6317 Mosaic somatic mutations in the isocitrate dehydrogenase 1/2 (IDH1/2) genes have been identified in most enchondromas by targeted mutation analysis. Next-generation sequencing (NGS), that may detect even low-level mosaic mutation rates, has not previously been applied to enchondromas. Immunohistochemistry using the H09 clone is routinely used as a surrogate for the common R132H IDH1 mutation in gliomas. We compared immunohistochemistry and NGS results in a series of 13 enchondromas from 8 pediatric patients. NGS identified a heterozygous IDH mutation in all enchondromas, showing identical mutation status in patients with multiple tumors assessed, thereby confirming somatic mosaicism. A majority of the tumors harbored an IDH1 mutation (p.R132H in 3 tumors; p.R132C in 4 tumors from 2 patients; p.R132L and p.R132G in one tumor each). A p.R172S IDH2 mutation was identified in 4 enchondromas, but not in the ependymoma from one patient with Ollier disease, who further displayed a heterozygous STK11 missense mutation. IDH mutation rates varied between 14% (indicative of mutations in 28% of the cells and of intratumoral mosaicism) and 45% (tumor content was close to 100%). Cytoplasmic H09 reactivity was observed as expected in tumors with an IDH1 p.R132H mutation; cross-reactivity was seen with the p.R132L variant. This first NGS study of pediatric enchondromas confirms that IDH mutations may occur in a mosaic fashion. STK11 gene mutations may provide insights in the development of multiple cartilaginous tumors in enchondromatosis, this tumor suppressor gene having been shown in animal models to regulate both chondrocyte maturation and growth plate organization during development. Dewey 616.07 Dewey 616.0757 Dewey 618 137 Département de pathologie et immunologie 21F 58 Département de pédiatrie, gynécologie et obstétrique 223 62 Département de radiologie et informatique médicale 227 false 564 Oncologie et hématologie pédiatriques 907 Virchows Archiv 9d10a83c-64da-4d3a-a792-bd0258b7990a Article (Published version) Restricted Article-6.pdf 4615708 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique Faculté de médecine / Section de médecine clinique / Département de radiologie et informatique médicale

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IDH1 immunohistochemistry reactivity and mosaic IDH1 or IDH2 somatic mutations in pediatric sporadic enchondroma and enchondromatosis	Virchows Archiv			2019	470	0

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Cerato, Christelle