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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-12-01
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| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.1001 |
| _version_ | 1827968016453730304 |
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| author | Michael Behring Ana I. Vazquez Xiangqin Cui Marguerite R. Irvin Akinyemi I. Ojesina Sumit Agarwal Upender Manne Sadeep Shrestha |
| author_facet | Michael Behring Ana I. Vazquez Xiangqin Cui Marguerite R. Irvin Akinyemi I. Ojesina Sumit Agarwal Upender Manne Sadeep Shrestha |
| author_sort | Michael Behring |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T18:14:39Z |
| format | Article |
| id | doaj.art-83a3ce23935b45a1a873a98a3be86944 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-09T18:14:39Z |
| publishDate | 2019-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-83a3ce23935b45a1a873a98a3be869442023-04-13T05:27:13ZengWileyMolecular Genetics & Genomic Medicine2324-92692019-12-01712n/an/a10.1002/mgg3.1001Gain of function in somatic TP53 mutations is associated with immune‐rich breast tumors and changes in tumor‐associated macrophagesMichael Behring0Ana I. Vazquez1Xiangqin Cui2Marguerite R. Irvin3Akinyemi I. Ojesina4Sumit Agarwal5Upender Manne6Sadeep Shrestha7Department of Epidemiology University of Alabama at Birmingham Birmingham AL USAInstitute for Quantitative Health Science and Engineering Michigan State University East Lansing MI USADepartment of Biostatistics and Bioinformatics Emory University Atlanta GA USADepartment of Epidemiology University of Alabama at Birmingham Birmingham AL USADepartment of Epidemiology University of Alabama at Birmingham Birmingham AL USADepartment of Pathology and Surgery University of Alabama at Birmingham Birmingham AL USADepartment of Pathology and Surgery University of Alabama at Birmingham Birmingham AL USADepartment of Epidemiology University of Alabama at Birmingham Birmingham AL USAAbstract 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.https://doi.org/10.1002/mgg3.1001breast cancerTP53 gain of functiontumor‐associated macrophagestumor‐invasive lymphocytes |
| spellingShingle | Michael Behring Ana I. Vazquez Xiangqin Cui Marguerite R. Irvin Akinyemi I. Ojesina Sumit Agarwal Upender Manne Sadeep Shrestha Gain of function in somatic TP53 mutations is associated with immune‐rich breast tumors and changes in tumor‐associated macrophages Molecular Genetics & Genomic Medicine breast cancer TP53 gain of function tumor‐associated macrophages tumor‐invasive lymphocytes |
| title | Gain of function in somatic TP53 mutations is associated with immune‐rich breast tumors and changes in tumor‐associated macrophages |
| title_full | Gain of function in somatic TP53 mutations is associated with immune‐rich breast tumors and changes in tumor‐associated macrophages |
| title_fullStr | Gain of function in somatic TP53 mutations is associated with immune‐rich breast tumors and changes in tumor‐associated macrophages |
| title_full_unstemmed | Gain of function in somatic TP53 mutations is associated with immune‐rich breast tumors and changes in tumor‐associated macrophages |
| title_short | Gain of function in somatic TP53 mutations is associated with immune‐rich breast tumors and changes in tumor‐associated macrophages |
| title_sort | gain of function in somatic tp53 mutations is associated with immune rich breast tumors and changes in tumor associated macrophages |
| topic | breast cancer TP53 gain of function tumor‐associated macrophages tumor‐invasive lymphocytes |
| url | https://doi.org/10.1002/mgg3.1001 |
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