While most driver genes had highly similar mutational frequencies across the three sites, the mutational frequencies of SIX2 and NOTCH2 were significantly higher in metastatic tumour samples than in primary tumour samples (Fig. 1c), suggesting that SIX2 and NOTCH2 might play an important role in NPC metastasis. This evidence concerns the gene SIX2 and nasopharyngeal carcinoma.