Data from The Cancer Genome Atlas (TCGA) has indicated that PIK3CA was the most commonly mutated oncogene in HPV-positive HNSCC, whereas genomic alterations in HPV-negative HNSCC were mostly limited to tumor suppressor genes, including TP53, NOTCH1, and FAT1 mutations and CDKN2A inactivation [58,77,78,79,80]. The gene discussed is FAT1; the disease is head and neck squamous cell carcinoma.