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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.
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.
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.
Shares Enasidenib, IDH1 / IDH2.
Shares Histopathology & immunohistochemistry, Comprehensive genomic profiling.
Shares Histopathology & immunohistochemistry, Comprehensive genomic profiling.
Shares Histopathology & immunohistochemistry, Comprehensive genomic profiling.
Shares Enasidenib, Sinonasal undifferentiated carcinoma (SNUC) and SWI/SNF-deficient sinonasal carcinoma, IDH1 / IDH2.
Shares Enasidenib, IDH1 / IDH2.
Shares Histopathology & immunohistochemistry, Comprehensive genomic profiling.
Shares Enasidenib, IDH1 / IDH2.