Identifying genetic modifiers in the tumor microenvironment using Consomic Xenograft Model

The majority of heritable breast cancer risk is unknown. One potential source of breast cancer heritability is genetic modifiers in the tumor microenvironment (TME). However, although genetic modifiers in the TME have long been suspected, they have rarely been studied and are largely unknown. We used the Consomic Xenograft Model (CXM) and RNA-seq to map genetic modifiers in the TME. In CXM, human breast cancer xenografts are implanted in immunodeficient consomic rat strains and tracked for tumor progression. Because the rat strains vary by one chromosome (i.e., consomic), whereas the malignant tumor cells do not differ, any observed changes in tumor phenotypes are due to genetic modifiers in the TME and can be localized to one chromosome.