However, novel inactivating mutations in NSD1 were identified in 29 of the 279 HNSCC tumors in the TCGA published in 2015 (all in HPV-negative tumors) [6], and the constellation of non-hotspot mutations suggest that this mutation, too, may be inactivating, potentially resulting in DNA hypomethylation. The gene discussed is NSD1; the disease is head and neck squamous cell carcinoma.