Frequent IDH2 R172 mutations in undifferentiated and poorly-differentiated sinonasal carcinomas.
Sinonasal undifferentiated carcinoma (SNUC) is a high-grade malignancy with limited treatment options and poor outcome. A morphological spectrum of 47 sinonasal tumours including 17 (36.2%) SNUCs was analysed at genomic level. Thirty carcinomas (cohort 1) were subjected to a hybridization exon-capture next-generation sequencing assay (MSK-IMPACTTM ) to interrogate somatic variants in 279 or 410 cancer-related genes. Seventeen sinonasal tumours (cohort 2) were examined only for the presence of IDH1/2 exon 4 mutations by Sanger sequencing. IDH2 R172 single nucleotide variants were overall detected in 14 (82.4%) SNUCs, in two (20%) poorly-differentiated carcinomas with glandular/acinar differentiation, and in one of two high-grade neuroendocrine carcinomas, large cell type (HGNECs). No IDH2 mutation was detected in any of five olfactory neuroblastomas or in any of five SMARCB1-deficient carcinomas. Among 12 IDH2-mutated cases in cohort 1, five (41.7%) harboured co-existing TP53 mutations, four (33.3%) CDKN2A/2B loss-of-function alterations, four (33.3%) MYC amplification, and three (25%) had concurrent SETD2 mutations. AKT1 E17K and KIT D816V hotspot variants were each detected in one IDH2-mutated SNUC. The vast majority of SNUCs and variable proportions of other poorly-differentiated sinonasal carcinomas may be amenable to IDH2-targeted therapy. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
['Dogan|Snjezana|S|0000-0002-4905-8946', 'Chute|Deborah J|DJ|', 'Xu|Bin|B|', 'Ptashkin|Ryan N|RN|', 'Chandramohan|Raghu|R|', 'Casanova-Murphy|Jacklyn|J|', 'Nafa|Khedoudja|K|', 'Bishop|Justin A|JA|', 'Chiosea|Simion I|SI|', 'Stelow|Edward B|EB|', 'Ganly|Ian|I|', 'Pfister|David G|DG|', 'Katabi|Nora|N|', 'Ghossein|Ronald A|RA|', 'Berger|Michael F|MF|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D014408:Biomarkers, Tumor D002277:Carcinoma D018278:Carcinoma, Neuroendocrine D018288:Carcinoma, Small Cell D004252:DNA Mutational Analysis D005260:Female D017353:Gene Deletion D016158:Genes, p53 D059014:High-Throughput Nucleotide Sequencing D006801:Humans D007521:Isocitrate Dehydrogenase D008297:Male D008444:Maxillary Sinus Neoplasms D008875:Middle Aged D009154:Mutation D000071796:SMARCB1 Protein
IDH2 R172 sinonasal undifferentiated carcinoma SNUC