TP53 and melanoma: Consistent with the landmark melanoma sequencing studies (primarily based on extracranial metastases),5,6 early melanoma brain metastases were dominated by a high mutational burden (with a predominance of C > T nucleotide transitions at dipyrimidines) and a similar frequency of the key driver mutations, including BRAF (42%), NRAS (28%), NF1 (22%) and TP53 (18%).