Gain of function in somatic TP53 mutations is associated with immune-rich breast tumors and changes in tumor-associated macrophages

Academic Article

Abstract

  • © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. Background: Somatic mutations in TP53 are present in 20%–30% of all breast tumors. While there are numerous population-based analyses of TP53, yet none have examined the relationship between somatic mutations in TP53 and tumor invasive immune cells. Methods: Clinical and genetic data from 601 women drawn from The Cancer Genome Atlas (TCGA) were used to test the association between somatic TP53 mutation and immune-rich or immune-poor tumor status; determined using the CIBERSORT-based gene expression signature of 22 immune cell types. Our validation dataset, the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), used a pathologist-determined measure of lymphocyte infiltration. Results: Within TP53-mutated samples, a mutation at codon p.R175H was shown to be present at higher frequency in immune-rich tumors. In validation analysis, any somatic mutation in TP53 was associated with immune-rich status, and the mutation at p.R175H had a significant association with tumor-invasive lymphocytes. TCGA-only analysis of invasive immune cell type identified an increase in M0 macrophages associated with p.R175H. Conclusions: These findings suggest that TP53 somatic mutations, particularly at codon p.R175H, are enriched in tumors with infiltrating immune cells. Our results confirm recent research showing inflammation-related gain of function in specific TP53 mutations.
  • Digital Object Identifier (doi)

    Author List

  • Behring M; Vazquez AI; Cui X; Irvin MR; Ojesina AI; Agarwal S; Manne U; Shrestha S
  • Volume

  • 7
  • Issue

  • 12