{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:33:51Z","timestamp":1791657231210,"version":"4.3.4"},"reference-count":40,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T00:00:00Z","timestamp":1718236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms25126518","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T03:52:53Z","timestamp":1718337173000},"page":"6518","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Methylation-Based Characterization of a New IDH2 Mutation in Sinonasal Undifferentiated Carcinoma"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1284-5284","authenticated-orcid":false,"given":"Simon","family":"Burgermeister","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Stoykova","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6291-7936","authenticated-orcid":false,"given":"Fanny S.","family":"Krebs","sequence":"additional","affiliation":[{"name":"Computer-Aided Molecular Engineering, Department of Oncology UNIL-CHUV, University of Lausanne, 1066 Epalinges, Switzerland"},{"name":"Ludwig Institute for Cancer Research, 1066 Epalinges, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2336-6537","authenticated-orcid":false,"given":"Vincent","family":"Zoete","sequence":"additional","affiliation":[{"name":"Computer-Aided Molecular Engineering, Department of Oncology UNIL-CHUV, University of Lausanne, 1066 Epalinges, Switzerland"},{"name":"Ludwig Institute for Cancer Research, 1066 Epalinges, Switzerland"},{"name":"Molecular Modelling Group, SIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martial","family":"Mbefo","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristof","family":"Egervari","sequence":"additional","affiliation":[{"name":"Service of Clinical Pathology, Department of Diagnostics, Geneva University Hospitals, 1206 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2420-9100","authenticated-orcid":false,"given":"Antoine","family":"Reinhard","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Lausanne University Hospital, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6840-375X","authenticated-orcid":false,"given":"Bettina","family":"Bisig","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9128-0364","authenticated-orcid":false,"given":"Ekkehard","family":"Hewer","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1038\/s41379-019-0285-x","article-title":"DNA methylation-based classification of sinonasal undifferentiated carcinoma","volume":"32","author":"Dogan","year":"2019","journal-title":"Mod. 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