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 journalArticle

19 Citations (Scopus)

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

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Carcinoma
Mutation
Exons
Olfactory Esthesioneuroblastoma
Neuroendocrine Carcinoma
Neoplasms
Neoplasm Genes
Nucleotides
Sinonasal undifferentiated carcinoma
Therapeutics

Keywords

  • IDH2 R172
  • sinonasal undifferentiated carcinoma
  • SNUC

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Dogan, S., Chute, D. J., Xu, B., Ptashkin, R. N., Chandramohan, R., Casanova-Murphy, J., ... Berger, M. F. (2017). Frequent IDH2 R172 mutations in undifferentiated and poorly-differentiated sinonasal carcinomas. Journal of Pathology, 242(4), 400-408. https://doi.org/10.1002/path.4915

Frequent IDH2 R172 mutations in undifferentiated and poorly-differentiated sinonasal carcinomas. / Dogan, Snjezana; Chute, Deborah J.; Xu, Bin; Ptashkin, Ryan N.; Chandramohan, Raghu; Casanova-Murphy, Jacklyn; Nafa, Khedoudja; Bishop, Justin A.; Chiosea, Simion I.; Stelow, Edward B.; Ganly, Ian; Pfister, David G.; Katabi, Nora; Ghossein, Ronald A.; Berger, Michael F.

In: Journal of Pathology, Vol. 242, No. 4, 01.08.2017, p. 400-408.

Research output: Contribution to journalArticle

Dogan, S, Chute, DJ, Xu, B, Ptashkin, RN, Chandramohan, R, Casanova-Murphy, J, Nafa, K, Bishop, JA, Chiosea, SI, Stelow, EB, Ganly, I, Pfister, DG, Katabi, N, Ghossein, RA & Berger, MF 2017, 'Frequent IDH2 R172 mutations in undifferentiated and poorly-differentiated sinonasal carcinomas', Journal of Pathology, vol. 242, no. 4, pp. 400-408. https://doi.org/10.1002/path.4915
Dogan S, Chute DJ, Xu B, Ptashkin RN, Chandramohan R, Casanova-Murphy J et al. Frequent IDH2 R172 mutations in undifferentiated and poorly-differentiated sinonasal carcinomas. Journal of Pathology. 2017 Aug 1;242(4):400-408. https://doi.org/10.1002/path.4915
Dogan, Snjezana ; Chute, Deborah J. ; Xu, Bin ; Ptashkin, Ryan N. ; Chandramohan, Raghu ; Casanova-Murphy, Jacklyn ; Nafa, Khedoudja ; Bishop, Justin A. ; Chiosea, Simion I. ; Stelow, Edward B. ; Ganly, Ian ; Pfister, David G. ; Katabi, Nora ; Ghossein, Ronald A. ; Berger, Michael F. / Frequent IDH2 R172 mutations in undifferentiated and poorly-differentiated sinonasal carcinomas. In: Journal of Pathology. 2017 ; Vol. 242, No. 4. pp. 400-408.
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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.",
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AU - Ganly, Ian

AU - Pfister, David G.

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