Expression data from primary breast tumors

Brain metastasis is one of the most feared complications of cancer and the most common intracranial malignancy in adults. Its underlying mechanisms remain unknown. From breast cancer patients with metastatic disease we isolated cell populations that aggressively colonize the brain. Transcriptomic analysis of these cells yielded overlapping gene sets whose expression is selectively associated with brain metastasis. The expression of seventeen of these genes in primary breast tumors is associated with brain relapse in breast cancer patients. Some of these genes are also associated with metastasis to lung but not to liver, bone or lymph nodes, providing a molecular basis for the long-observed link between brain and lung metastasis. Among the functionally validated brain metastasis genes, the cyclooxigenase COX-2, the EGFR ligand HB-EGF, and the brain-specific 2-6 sialyltransferase ST6GALNAC5 mediate cancer cell passage through the blood-brain barrier. Other brain metastasis genes encode inflammatory factors and brain-specific proteolytic regulators, suggesting a multifaceted program for breast cancer colonization of the brain. Keywords: Disease state comparison 204 primary tumors from breast cancer patients with known site of relapse were studied, focussing on brain relapse versus other relapse. Identified genes were validated in this cohort.