Extended Data Fig. 3: Comparison of colon and rectal adenocarcinomas.

(a) Clinicopathological features for right colon, left colon, and rectum samples. (b) Differences in first site of metastasis stratified by primary tumor ___location. (c) Tumor mutational burden (TMB) and FGA in pMMR/MSS tumors from the right colon (n = 121), left colon (n = 187), and rectum (n = 449). Statistical significance was assessed using a two-sided Mann–Whitney U-test. (d) Frequency of somatic alterations in oncogenic signaling pathways by anatomic ___location. Significant results were denoted as * indicating q < 0.05, ** indicating q < 0.01, *** indicating q < 0.005, and **** indicating q < 0.001. (e) Frequency of RAS/RAF alterations in hypermutated and non-hypermutated tumors stratified by tumor ___location. (f) Copy number profiles for tumors in the analyzed cohorts. (g) Frequency of copy number alterations affecting the p and q arms of chromosome 20 by anatomic ___location. (h) FGA as a function of TP53 status, stratified by missense versus truncating and mono-allelic versus biallelic inactivation, for tumors from the right colon (wild-type n = 39, missense n = 8, missense biallelic n = 33, truncating n = 1, truncating biallelic n = 17), left colon (wild-type n = 32, missense n = 10, missense biallelic n = 77, truncating n = 5, truncating biallelic n = 29) and rectum (wild-type n = 73, missense n = 44, missense biallelic n = 175, truncating n = 12, truncating biallelic n = 81). (i) Fraction of dMMR/MSI tumors by rectal segment. (j) Distance to the anal verge by APC status in the validation cohort of metastatic patients. APC WT (n = 43) were compared to APC altered (n = 115) using a two-sided Mann–Whitney U-test, * indicates p = 0.0029. (k) Distribution of APC mutations by genomic ___location in tumors from the right colon, left colon, upper rectum, middle rectum, and lower rectum. In panels (B), (D) and (G), statistical significance was assessed using a two-sided Fisher’s exact test and p values were corrected for multiple testing using false discovery rate. In panels (C), (H) and (J), boxplots’ center lines indicate medians, edges indicate the interquartile range, and whiskers extend to the highest and lowest values not considered outliers.