TP53 and cancer: The first studies linking specific mutation characteristics to various environmental mutagens, such as UV-radiation [18], smoking [19], and aristolochic acid [20], were focused on single cancer genes that were recurrently mutated in a wide range of cancers, such as TP53 and BRAF. These studies provided the first evidence that mutational processes can leave characteristic patterns in the DNA that are visible and analyzable in tumor samples via the detection of distinct signatures [21].