Recurrent differential expression of open reading frames on chromosome 14 in human metastatic breast cancer.
Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We leveraged the power of systems-level comparative transcriptome analysis in human tissues to discover genes associated with brain metastasis in human breast cancer by integration of multiple independent published microarray datasets (4-7). We identified five independent open reading frames on chromosome 14 that were among the most differentially expressed, transcriptome-wide, in the brain metastatic tissues of patients with metastatic breast cancer when compared to primary tumors of the breast: C14orf179, C14orf112, C14orf169, C14orf109 and C14orf130. Importantly, primary tumor expression of each of these open reading frames was significantly correlated with either overall, distant metastasis-free, or recurrence-free survival in patients with breast cancer. Analysis of three separate microarray datasets revealed at least five other open reading frames on chromosome 14 that were recurrently transcriptionally modulated in brain metastatic tissues of humans with metastatic breast cancer as evidenced by transcriptome-wide differential expression relative to primary tumors of the breast. It is possible that structural or epigenetic changes on chromosome 14 are a major feature associated with human brain metastatic breast cancer.