Unknown

Dataset Information

0

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


ABSTRACT: 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.

SUBMITTER: Behring M 

PROVIDER: S-EPMC6900370 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Behring Michael M   Vazquez Ana I AI   Cui Xiangqin X   Irvin Marguerite R MR   Ojesina Akinyemi I AI   Agarwal Sumit S   Manne Upender U   Shrestha Sadeep S  

Molecular genetics & genomic medicine 20191022 12


<h4>Background</h4>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.<h4>Methods</h4>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  ...[more]

Similar Datasets

| S-EPMC10134541 | biostudies-literature
| S-EPMC5323125 | biostudies-literature
| S-EPMC5088513 | biostudies-literature
| S-EPMC5689569 | biostudies-literature
| S-EPMC4936490 | biostudies-literature
| S-EPMC6110754 | biostudies-other
| S-EPMC9816166 | biostudies-literature
| S-EPMC5584393 | biostudies-literature
| S-EPMC8505454 | biostudies-literature
| S-EPMC2865889 | biostudies-other