Extended Data Fig. 1: Absence of tamoxifen-induced mutagenesis in TA-UC.

(a) CONSORT flow diagram depicts allocation of Netherlands Cancer Institute (NKI) patients from the TAMARISK study for our analysis. (b) Bar plot of uterine cancer (UC) cohorts with and without history of tamoxifen (TA); bars represent histological type frequencies (endom., endometrial); error bars reflect standard deviation from the β-distribution; significance analysis by two-sided Fisher’s exact test with Benjamini-Hochberg procedure; numbers in/above bars indicate tumor count per group. (c) Bar plot of TA-UC and de novo UC cases (excluding 7 endometroid and 4 serous endometrial TCGA tumors due to lack of annotation); bars represent molecular subtype frequencies; error bars reflect standard deviation from the β-distribution; numbers in bars indicate tumor count per group. Significance analysis by two-sided Fisher’s exact test with Benjamini-Hochberg procedure (CIN, chromosomal instable; GS, genomically stable; MSI, microsatellite instability; POLE, polymerase ε). (d) MSI scores for each TA-UC sample (dots), generated by MSIDetect (see Methods); corresponding normal samples served as controls; tumors with a higher score than in the normal were classified as MSI cases. (e) Number of non-synonymous mutations per exome (mutations/Megabase, left) and fraction of chromosomal regions affected by ABSOLUTE somatic copy number alterations (SCNAs) out of all measured regions (right); dots represent single samples; horizontal lines indicate group medians. Significance analysis by two-sided Wilcoxon test. (f) Number of non-synonymous mutations grouped by molecular subtype as in c. Individual data points (black) overlay summary statistic boxplots; horizontal center lines indicate median; boxes span the interquartile range (IQR, 25th to 75th percentile); whiskers extend to the most extreme values within 1.5×IQR. Significance analysis by two-sided Wilcoxon test with Benjamini-Hochberg procedure. (g) Number of chromosomal regions affected by somatic copy number alterations (that is, amplifications and deletions; top) or deletions only (bottom), grouped by molecular subtypes as in c. Individual data points (black) overlay summary statistic boxplots; horizontal center lines indicate median; boxes span the interquartile range (IQR, 25th to 75th percentile); whiskers extend to the most extreme values within 1.5×IQR. Significance analysis by two-sided Wilcoxon test with Benjamini-Hochberg procedure.