Abstract IA21: An integrated genome-wide systems genetics screen for breast cancer metastasis susceptibility genes

Abstract

Abstract Metastasis remains the primary cause of patient morbidity and mortality in solid tumors and is due to the action of a large number of tumor-autonomous and non-autonomous factors. Hundreds or thousands of genes are thought to be associated with metastasis however how many of these genes contribute etiologically to tumor progression is not currently known. Identification of the genes contributing mechanistically to the metastatic processes will not only deepen our understanding of how metastases occur, but also provide novel targets for either preventing their formation or combatting their life-threatening effects. Previously our laboratory demonstrated that inbred mice of distinct phylogenetic lineages possess distinct propensity for metastatic disease, indicating that inherited susceptibility for metastasis exists and that polymorphisms can both mark and functionally effect genes within the metastatic cascade. Here we report the results of a genome-wide integrated strategy to identify novel metastasis susceptibility candidate genes and molecular pathways which implicates a number of transcriptional regulators and suggests cell-mediated immunity is an important determinant. The strategy described integrates meiotic genetic screens with epigenetic control of gene expression and three dimensional chromatin structure analyses to identify genes, molecular and cellular pathways likely to be important in metastatic disease. Moreover, the analysis identified novel or FDA-approved drugs as potentially useful for anti-metastatic therapy. Further explorations implementing this strategy may therefore provide a variety of information for clinical applications in the control and treatment of advanced neoplastic disease. Citation Format: Kent W. Hunter, Ling Bai, Howard H. Yang, Ying Hu, Anjali Shukla, Ngoc-Han Ha, Anthony Doran, Farhoud Faraji, Natalie Goldberger, Maxwell P. Lee, Thomas Keane. An integrated genome-wide systems genetics screen for breast cancer metastasis susceptibility genes. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr IA21.