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Abstract P6-06-06: Immunogenomics approach elucidating clinical significance of DNA repair genes and tumor infiltrating immune cells in breast cancer

Backgrounds: Evading the immune system is one of the Hallmarks of Cancer. Indeed, tumor infiltrating immune cells has been shown to play critical roles in suppression of cancer progression. Genetic… Click to show full abstract

Backgrounds: Evading the immune system is one of the Hallmarks of Cancer. Indeed, tumor infiltrating immune cells has been shown to play critical roles in suppression of cancer progression. Genetic aberration of DNA repair genes is known to increase immunogenicity in breast cancer. However, the patient survival relevance of tumor infiltrating immune cells in regard to DNA repair genes has not yet elucidated in large cohort of breast cancer patients. We hypothesized that DNA repair gene deficiency is related to increased global genomic instability that leads to increased mutation burden, which recruits infiltrating immune cells to tumor microenvironment that result in better prognosis of breast cancer. Patients and Methods: Integrated and unbiased transcriptomics approach was conducted on genomic and clinicopathological information of 3614 breast cancer patients. We utilized The cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) to evaluate the association between the aberration of DNA repair genes and tumor infiltrating immune cell composition in breast cancer tumors, as well as its significant clinical relevance, utilizing bioinformatics and biostatistics pipelines. Results:Low expression level of double-strand break repair genes; BRCA1, PRKDC, and RECQL4,demonstrated significantlybetter prognosis in TCGA cohort (p=0.018, p=0.036, and p=0.0002, respectively). This result was consistent in METABRIC cohort (p=0.021, p=0.00021, and p Conclusions: We conclude that our immunogenomics approach identify the interplay between DNA repair genes, especially gene expression of BRCA1, and tumor infiltrating immune cells, and it could have significant prognostic relevance in breast cancer. Citation Format: Takabe K, Kawaguchi T, Yan L, Peng X, Qi Q, Okano M, Young J, Liu S. Immunogenomics approach elucidating clinical significance of DNA repair genes and tumor infiltrating immune cells in breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-06-06.

Keywords: dna repair; breast cancer; infiltrating immune; cancer; repair genes

Journal Title: Cancer Research
Year Published: 2018

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