8p Loss of Heterozygosity triggers metastasis and drug resistance. Homo sapiens

Chromosome arm deletions are frequently observed in human cancers. Such large-scale aberrations may trigger phenotypes distinct from those that arise by loss of single genes. Using TALEN-based genomic engineering, we generated cell models with targeted 8p loss-of-heterozygosity (LOH) that mimics an 8p deletion commonly found in breast cancer patients. 8p LOH triggered up-regulation of the mevalonate pathway. The alterations in lipid metabolism led to increased metastatic potential and drug resistance of 8p-deleted cells that are in agreement with poorer survival rates of breast cancer patients harbouting 8p LOH. Our findings also suggest novel therapeutic strategies for treatment of 8p LOH tumors. Overall design: RNASeq Analysis of two Wt 8p Cell clones vs two 8p LOH cell clones generated via TALEN Approach