Molecular signature associated with bone marrow micrometastasis in human breast cancer

Metastasis is the leading cause of cancer-related death, and bone marrow (BM) is a prominent metastatic site in solid tumors. Here, we focused on the onset of metastasis, using BM as an indicator organ for micrometastatic tumor cells in breast cancer patients without overt metastases (tumor-node-metastasis stage M(0)). Expression analysis with cDNA arrays showed distinct profiles between primary tumors from BM-positive and BM-negative patients. The differentially expressed genes are involved in extracellular matrix remodeling, adhesion, cytoskeleton plasticity, and signal transduction (in particular RAS and hypoxia-inducible factor 1alpha pathway). The BM signature was mainly characterized by transcriptional repression and different from the expression signature associated with lymphatic metastasis. Thus, BM micrometastasis is a selective process with a specific molecular signature of the primary tumor.