Differences in somatic TP53 mutation type in breast tumors by race and receptor status

Nijole C. Pollock, Johnny R. Ramroop, Heather Hampel, Melissa A. Troester, Kathleen Conway, Jennifer J. Hu, Jo L. Freudenheim, Olufunmilayo I. Olopade, Dezheng Huo, Elad Ziv, Susan L. Neuhausen, Patrick Stevens, Joseph Paul McElroy, Amanda Ewart Toland

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Somatic driver mutations in TP53 are associated with triple-negative breast cancer (TNBC) and poorer outcomes. Breast cancers in women of African ancestry (AA) are more likely to be TNBC and have somatic TP53 mutations than cancers in non-Hispanic White (NHW) women. Missense driver mutations in TP53 have varied functional impact including loss-of-function (LOF) or gain-of-function (GOF) activity, and dominant negative (DNE) effects. We aimed to determine if there were differences in somatic TP53 mutation types by patient ancestry or TNBC status. Methods: We identified breast cancer datasets with somatic TP53 mutation data, ancestry, age, and hormone receptor status. Mutations were classified for functional impact using published data and type of mutation. We assessed differences using Fisher’s exact test. Results: From 96 breast cancer studies, we identified 2964 women with somatic TP53 mutations: 715 (24.1%) Asian, 258 (8.7%) AA, 1931 (65.2%) NHW, and 60 (2%) Latina. The distribution of TP53 mutation type was similar by ancestry. However, 35.8% of tumors from NHW individuals had GOF mutations compared to 29% from AA individuals (p = 0.04). Mutations with DNE activity were positively associated with TNBC (OR 1.37, p = 0.03) and estrogen receptor (ER) negative status (OR 1.38; p = 0.005). Conclusions: Somatic TP53 mutation types did not differ by ancestry overall, but GOF mutations were more common in NHW women than AA women. ER-negative and TNBC tumors are less likely to have DNE+ TP53 mutations which could reflect biological processes. Larger cohorts and functional studies are needed to further elucidate these findings.

Original languageEnglish (US)
Pages (from-to)639-648
Number of pages10
JournalBreast cancer research and treatment
Volume192
Issue number3
DOIs
StatePublished - Apr 2022
Externally publishedYes

Keywords

  • Breast cancer
  • Dominant negative
  • Gain-of-function
  • Loss-of-function
  • Racial differences
  • TP53

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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