# Recurrent IDH2 R172X mutations in sinonasal undifferentiated carcinoma

Source: https://onco.cc/key-papers/paper-jo-idh2-r172-mutations-snuc-mod-pathol-2017/  
OnCo record `paper-jo-idh2-r172-mutations-snuc-mod-pathol-2017` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Sequencing showed that most sinonasal undifferentiated carcinomas, a cancer long defined only by what it is not, carry a mutation in the IDH2 gene found in no other head and neck cancer, giving the disease a molecular identity, a diagnostic antibody test and a possible drug target.

## Summary

Targeted next-generation sequencing of 300 cancer-related genes in 11 sinonasal undifferentiated carcinomas from Brigham and Women's Hospital and Dana-Farber Cancer Institute. IDH2 R172 mutations (R172S, R172T and R172M) were found in 55 percent of cases, and a multispecific mutant IDH1/2 antibody stained all mutant tumours with available tissue (3 of 3) and none of the wild-type (0 of 4). Review of 412 sequenced head and neck tumours at the same institutions found IDH-activating mutations in no other tumour type.

IDH2 wild-type cases carried SMARCA4 loss with loss of protein expression, NOTCH1 gain-of-function or TET2 loss-of-function alterations, foreshadowing the later separation of SWI/SNF-deficient sinonasal carcinoma. Published alongside a Memorial Sloan Kettering series with the same finding, the paper established IDH2 R172 as the defining alteration of the disease.

## Fields

- Kind: Key paper
- Last checked: 2026-09-18
- Journal: Modern Pathology
- Year: 2017
- DOI: 10.1038/modpathol.2016.239
- Authors: Jo VY, Chau NG, Hornick JL, Krane JF, Sholl LM.
- Findings: IDH2 R172 mutations in 55 percent of 11 sinonasal undifferentiated carcinomas (R172S, R172T, R172M).; Mutant IDH1/2 immunohistochemistry was positive in 3 of 3 mutant and negative in 4 of 4 wild-type tumours.; No IDH-activating mutation in 412 other head and neck tumours; IDH2 wild-type cases showed SMARCA4, NOTCH1 or TET2 alterations.
- What it means: Sinonasal undifferentiated carcinoma can be confirmed by IDH2 testing or mutant-IDH immunohistochemistry rather than diagnosed by exclusion, and IDH2 inhibitors such as enasidenib became rational candidates for trials.
- Caveats: Eleven cases from two institutions; later series put the IDH2 mutation rate at roughly 50 to 80 percent.; Diagnostic value rests on the mutation being absent from mimics, which larger cohorts have since confirmed for carcinomas but not for a subset of high-grade esthesioneuroblastomas.

## Sources

- Mod Pathol 2017: https://doi.org/10.1038/modpathol.2016.239
- PubMed: https://pubmed.ncbi.nlm.nih.gov/28084339/

## Connected records

- cancers: [Sinonasal undifferentiated carcinoma (SNUC) and SWI/SNF-deficient sinonasal carcinoma](https://onco.cc/cancers/sinonasal-undifferentiated-carcinoma/)
- technologies: [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/)
- targets: [IDH1 / IDH2](https://onco.cc/targets/idh/)
- drugs: [Enasidenib](https://onco.cc/drugs/enasidenib/)

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