Frequent IDH2 R172 mutations in undifferentiated and poorly-differentiated sinonasal carcinomas Journal Article
| Authors: | Dogan, S.; Chute, D. J.; Xu, B.; Ptashkin, R. N.; Chandramohan, R.; Casanova-Murphy, J.; Nafa, K.; Bishop, J. A.; Chiosea, S. I.; Stelow, E. B.; Ganly, I.; Pfister, D. G.; Katabi, N.; Ghossein, R. A.; Berger, M. F. |
| Article Title: | Frequent IDH2 R172 mutations in undifferentiated and poorly-differentiated sinonasal carcinomas |
| Abstract: | 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. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
| Keywords: | sinonasal undifferentiated carcinoma; idh2 r172; snuc |
| Journal Title: | Journal of Pathology |
| Volume: | 242 |
| Issue: | 4 |
| ISSN: | 0022-3417 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2017-08-01 |
| Start Page: | 400 |
| End Page: | 408 |
| Language: | English |
| DOI: | 10.1002/path.4915 |
| PROVIDER: | scopus |
| PUBMED: | 28493366 |
| PMCID: | PMC5639875 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 August 2017 -- Source: Scopus |
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