Mutations in components of antiviral or microbial defense as a basis for breast cancer.

In-depth functional analyses of thousands of breast cancer gene mutations reveals vastly different sets of mutated genes in each of 21 different breast cancer genomes. Despite differences in which genes are mutated, innate immunity pathways and metabolic reactions supporting them are always damaged. These functions depend on many different genes. Mutations may be rare individually but each set of mutations affects some aspect of pathogen recognition and defense, especially those involving viruses. Some mutations cause a dysregulated immune response, which can also increase cancer risks. The frequency of an individual mutation may be less important than its effect on function. This work demonstrates that acquired immune deficiencies and immune dysregulation in cancer can occur because of mutations. Abnormal immune responses represent a hidden variable in breast cancer-viral association studies. Compensating for these abnormalities may open many new opportunities for cancer prevention and therapy.