Frequent IDH2 R172 mutations in undifferentiated and poorly-differentiated sinonasal carcinomas

Snjezana Dogan, Deborah J. Chute, Bin Xu, Ryan N. Ptashkin, Raghu Chandramohan, Jacklyn Casanova-Murphy, Khedoudja Nafa, Justin A. Bishop, Simion I. Chiosea, Edward B. Stelow, Ian Ganly, David G. Pfister, Nora Katabi, Ronald A. Ghossein, Michael F. Berger

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)400-408
Number of pages9
JournalJournal of Pathology
Volume242
Issue number4
DOIs
StatePublished - Aug 1 2017

Keywords

  • IDH2 R172
  • sinonasal undifferentiated carcinoma
  • SNUC

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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