Methylation-Based Characterization of a New IDH2 Mutation in Sinonasal Undifferentiated Carcinoma

Article Article scientifique Rapport de cas Methylation-Based Characterization of a New IDH2 Mutation in Sinonasal Undifferentiated Carcinoma eng 2024-06-13 2024-06-13 author Burgermeister Simon 0000-0002-1284-5284 Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland. author Stoykova Simona Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland. author Krebs Fanny S 0000-0002-6291-7936 Computer-Aided Molecular Engineering, Department of Oncology UNIL-CHUV, University of Lausanne, 1066 Epalinges, Switzerland.,Ludwig Institute for Cancer Research, 1066 Epalinges, Switzerland. author Zoete Vincent 0000-0002-2336-6537 Computer-Aided Molecular Engineering, Department of Oncology UNIL-CHUV, University of Lausanne, 1066 Epalinges, Switzerland.,Ludwig Institute for Cancer Research, 1066 Epalinges, Switzerland.,Molecular Modelling Group, SIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland. author Mbefo Martial Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland. author Egervari Kristof Levente 0000-0001-6763-9069 Service of Clinical Pathology, Department of Diagnostics, Geneva University Hospitals, 1206 Geneva, Switzerland. 761273 author Reinhard Antoine 0000-0003-2420-9100 Department of Otorhinolaryngology-Head and Neck Surgery, Lausanne University Hospital, 1011 Lausanne, Switzerland. 652196 author Bisig Bettina 0000-0002-6840-375X Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland. author Hewer Ekkehard 0000-0002-9128-0364 Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland. 6518 10.3390/ijms25126518 38928223 1422-0067 PMC11204065 https://www.mdpi.com/1422-0067/25/12/6518 Mutations affecting codon 172 of the isocitrate dehydrogenase 2 (IDH2 ) gene define a subgroup of sinonasal undifferentiated carcinomas (SNUCs) with a relatively favorable prognosis and a globally hypermethylated phenotype. They are also recurrent (along with IDH1 mutations) in gliomas, acute myeloid leukemia, and intrahepatic cholangiocarcinoma. Commonly reported mutations, all associated with aberrant IDH2 enzymatic activity, include R172K, R172S, R172T, R172G, and R172M. We present a case of SNUC with a never-before-described IDH2 mutation, R172A. Our report compares the methylation pattern of our sample to other cases from the Gene Expression Omnibus database. Hierarchical clustering suggests a strong association between our sample and other IDH-mutant SNUCs and a clear distinction between sinonasal normal tissues and tumors. Principal component analysis (PCA), using 100 principal components explaining 94.5% of the variance, showed the position of our sample to be within 1.02 standard deviation of the other IDH-mutant SNUCs. A molecular modeling analysis of the IDH2 R172A versus other R172 variants provides a structural explanation to how they affect the protein active site. Our findings thus suggest that the R172A mutation in IDH2 confers a gain of function similar to other R172 mutations in IDH2 , resulting in a similar hypermethylated profile. IDH2 mutation Methylation analysis Molecular modeling Humans Isocitrate Dehydrogenase / genetics DNA Methylation / genetics Carcinoma / genetics Carcinoma / pathology Mutation Maxillary Sinus Neoplasms / genetics Maxillary Sinus Neoplasms / pathology Male Middle Aged Female Aged Dewey 616.07 137 Département de pathologie et immunologie 21F false International journal of molecular sciences 25 12 37260d21-ea2a-4e2d-b3f7-40c15e78aed9 Article (Published version) Public Article_scientifique_from_unpaywall.pdf 11138564 application/pdf CC BY-4.0 5bf37ef857017d3a93126ff3d52db06000dc51f1b48868c5aa60b4b5e28b1cad openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Methylation-Based Characterization of a New IDH2 Mutation in Sinonasal Undifferentiated Carcinoma	International journal of molecular sciences			2024	52	86

Archive ouverte UNIGE

Reinhard, Antoine