(A) Distribution of TP53 nonsense (top, black) and missense (bottom, green) mutations in the TCGA cohort (n = 2521 tumors). Domains are demarcated on the upper baseline as follows: trans-activating domains (orange), Proline rich domain (green), DNA binding domain (light blue), nuclear localization sequence (yellow), and oligomerization domain (purple). The lower baseline and Roman numerals below indicate TP53 exon location relative to the p53 coding sequence. (B) Analysis as in A in the MSKCC cohort (n = 3797 tumors). (C–D) Recurrence frequency of each mutation type per unique change per sample in the TCGA and MSKCC cohorts respectively (Missense, p<2.2e-16; other nonsense, p=0.00178 and exon-6 nonsense, p=3.869e-11, Fisher’s exact test). (E) Count of unique reported amino acid changes and observed instances of exon-6 nonsense, other nonsense, missense, or all mutations. (F) Frequency of TP53 alteration vs. frequency of TP53 truncating mutations by cancer type. Circles were plotted in proportion to the frequency of TP53 exon-6 truncation mutations. See Supplementary file 1 for cancer type abbreviations. (G) The pie charts represent the relative frequency of TP53 mutation type for colorectal cancer primary tumors (top left, n = 403) and metastases (top right, n = 395). Mutations are indicated as follows: splice site mutations (Splice, light blue, p=0.035, fisher’s exact test), exon-6 nonsense mutation (Ex6 NS, orange, p=0.041), other nonsense mutation (Other NS, pink), in-frame insertion/deletion (IF indel, yellow), frameshift insertion/deletion (FS indel, gold), missense mutation (MS, green), multiple mutations (Multiple, purple), or no TP53 mutation (None, white). Note that both exon-6 nonsense mutations (p-value = 0.041) and missense mutations (p-value = 0.035) are over-represented in the metastatic samples with respect to p53-WT cases, whereas nonsense mutations outside of exon-6 and missense mutations are not (Fisher's exact test). The lower chart indicates the ratio of frequency in metastases to primary colorectal cancers of the indicated TP53 mutations. See Supplementary file 3 for number of tumor samples with TP53 mutation in primary CRC and metastatic CRC.