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• W4229453013 abstract "Abstract Both TP53 and ESR1 mutations occur frequently in estrogen receptor positive (ER+) metastatic breast cancers (MBC) and their distinct roles in breast cancer tumorigenesis and progression are well appreciated. Recent clinical studies discovered mutual exclusivity between TP53 and ESR1 mutations in metastatic breast cancers; however, mechanisms underlying this intriguing clinical observation remain largely understudied and unknown. Here, we explored the interplay between TP53 and ESR1 mutations using publicly available clinical and experimental data sets. We first confirmed the robust mutational exclusivity using six independent cohorts with 1,056 ER+ MBC samples and found that the exclusivity broadly applies to all ER+ breast tumors regardless of their clinical and distinct mutational features. ESR1 mutant tumors do not exhibit differential p53 pathway activity, whereas we identified attenuated ER activity and expression in TP53 mutant tumors, driven by a p53-associated E2 response gene signature. Further, 81% of these p53-associated E2 response genes are either direct targets of wild-type (WT) p53-regulated transactivation or are mutant p53-associated microRNAs, representing bimodal mechanisms of ER suppression. Lastly, we analyzed the very rare cases with co-occurrences of TP53 and ESR1 mutations and found that their simultaneous presence was also associated with reduced ER activity. In addition, tumors with dual mutations showed higher levels of total and PD-L1 positive macrophages. In summary, our study utilized multiple publicly available sources to explore the mechanism underlying the mutual exclusivity between ESR1 and TP53 mutations, providing further insights and testable hypotheses of the molecular interplay between these two pivotal genes in ER+ MBC." @default.
• W4229453013 created "2022-05-11" @default.
• W4229453013 creator A5002309098 @default.
• W4229453013 creator A5011384968 @default.
• W4229453013 creator A5028610485 @default.
• W4229453013 creator A5041977512 @default.
• W4229453013 creator A5073085049 @default.
• W4229453013 date "2022-05-10" @default.
• W4229453013 modified "2023-10-15" @default.
• W4229453013 title "Mutual exclusivity of ESR1 and TP53 mutations in endocrine resistant metastatic breast cancer" @default.
• W4229453013 cites W1769240683 @default.
• W4229453013 cites W1799492544 @default.
• W4229453013 cites W1934888046 @default.
• W4229453013 cites W1965641017 @default.
• W4229453013 cites W1970195561 @default.
• W4229453013 cites W1970431885 @default.
• W4229453013 cites W1979206664 @default.
• W4229453013 cites W2003577093 @default.
• W4229453013 cites W2005563089 @default.
• W4229453013 cites W2006024897 @default.
• W4229453013 cites W2013721931 @default.
• W4229453013 cites W2024265215 @default.
• W4229453013 cites W2033581856 @default.
• W4229453013 cites W2041908101 @default.
• W4229453013 cites W2043398720 @default.
• W4229453013 cites W2056302937 @default.
• W4229453013 cites W2078692783 @default.
• W4229453013 cites W2081949499 @default.
• W4229453013 cites W2088835619 @default.
• W4229453013 cites W2094160175 @default.
• W4229453013 cites W2094420610 @default.
• W4229453013 cites W2107281049 @default.
• W4229453013 cites W2114843025 @default.
• W4229453013 cites W2122387572 @default.
• W4229453013 cites W2123649978 @default.
• W4229453013 cites W2131132514 @default.
• W4229453013 cites W2131604549 @default.
• W4229453013 cites W2140593657 @default.
• W4229453013 cites W2141280707 @default.
• W4229453013 cites W2147533449 @default.
• W4229453013 cites W2151483495 @default.
• W4229453013 cites W2155826575 @default.
• W4229453013 cites W2159707944 @default.
• W4229453013 cites W2162149241 @default.
• W4229453013 cites W2166869851 @default.
• W4229453013 cites W2177855755 @default.
• W4229453013 cites W2178157469 @default.
• W4229453013 cites W2180834397 @default.
• W4229453013 cites W2214074259 @default.
• W4229453013 cites W2236415406 @default.
• W4229453013 cites W2237475663 @default.
• W4229453013 cites W2270544154 @default.
• W4229453013 cites W2290208632 @default.
• W4229453013 cites W2298001438 @default.
• W4229453013 cites W2343983168 @default.
• W4229453013 cites W2413839170 @default.
• W4229453013 cites W2416423710 @default.
• W4229453013 cites W2464072555 @default.
• W4229453013 cites W2569913966 @default.
• W4229453013 cites W2570752636 @default.
• W4229453013 cites W2583621343 @default.
• W4229453013 cites W2592811885 @default.
• W4229453013 cites W2607628501 @default.
• W4229453013 cites W2619213753 @default.
• W4229453013 cites W2741363425 @default.
• W4229453013 cites W2755290882 @default.
• W4229453013 cites W2756562465 @default.
• W4229453013 cites W2758629197 @default.
• W4229453013 cites W2784814401 @default.
• W4229453013 cites W2786726389 @default.
• W4229453013 cites W2788302995 @default.
• W4229453013 cites W2790152406 @default.
• W4229453013 cites W2792578813 @default.
• W4229453013 cites W2792951836 @default.
• W4229453013 cites W2802013111 @default.
• W4229453013 cites W2804549383 @default.
• W4229453013 cites W2885841563 @default.
• W4229453013 cites W2891371951 @default.
• W4229453013 cites W2891700678 @default.
• W4229453013 cites W2898440040 @default.
• W4229453013 cites W2901027836 @default.
• W4229453013 cites W2911625234 @default.
• W4229453013 cites W2912993657 @default.
• W4229453013 cites W2944883972 @default.
• W4229453013 cites W2976511826 @default.
• W4229453013 cites W2979439917 @default.
• W4229453013 cites W2982128568 @default.
• W4229453013 cites W3005327280 @default.
• W4229453013 cites W3012232812 @default.
• W4229453013 cites W3012748963 @default.
• W4229453013 cites W3014679264 @default.
• W4229453013 cites W3015289091 @default.
• W4229453013 cites W3015634062 @default.
• W4229453013 cites W3024627825 @default.
• W4229453013 cites W3024744974 @default.
• W4229453013 cites W3041255266 @default.
• W4229453013 cites W3048604521 @default.
• W4229453013 cites W3083605593 @default.
• W4229453013 cites W3102914996 @default.
• W4229453013 cites W3105282488 @default.

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