Fusion Genes in Breast Cancer

Fusion gene is a hybrid form of two distinct genes resulting in broad spectrum of downstream pathway alterations. Gene fusion events are mostly from genomic rearrangements though diverse mechanisms have now been identified from in-depth analyses of next generation sequencing data. While profound level of genomic, transcriptomic driver alterations have been identified, till now, not many gene fusions are found to be the 'driver' of cancer development nor progression.ESR1 gene is a protein coding gene, encoding estrogen receptor, a transcription factor which is a key pathway in hormone sensitive breast cancers. Several hotspot mutations of this ESR1 gene have recently been associated with resistance to endocrine therapy. ESR1 gene fusion with diverse partner genes have also been identified recently, and are suggested to be acquired during previous endocrine therapy. Recurrent ESR1 gene fusions are indicative of ligand-independent hyperactivity according to 3' partner gene found among 1%~ of metastatic hormone sensitive metastatic breast cancers.