Genomic hotspots but few recurrent fusion genes in breast cancer

Genes Chromosomes Cancer. 2018 Jul;57(7):331-338. doi: 10.1002/gcc.22533. Epub 2018 Mar 22.


The advent of next generation sequencing technologies has boosted the interest in exploring the role of fusion genes in the development and progression of solid tumors. In breast cancer, most of the detected gene fusions seem to be "passenger" events while the presence of recurrent and driver fusions is still under study. We performed RNA sequencing in 55 well-characterized breast cancer samples and 10 adjacent normal breast tissues, complemented by an analysis of SNP array data. We explored the presence of fusion genes and defined their association with breast cancer subtypes, clinical-pathologic characteristics and copy number aberrations. Overall, 370 fusions were detected across the majority of the samples. HER2+ samples had significantly more fusions than triple negative and luminal subtypes. The number of fusions was correlated with histological grade, Ki67 and tumor size. Clusters of fusion genes were observed across the genome and a significant correlation of fusions with copy number aberrations and more specifically amplifications was also revealed. Despite the large number of fusion events, only a few were recurrent, while recurrent individual genes forming fusions with different partners were also detected including the estrogen receptor 1 gene in the previously detected ESR1-CCDC170 fusion. Overall we detected novel gene fusion events while we confirmed previously reported fusions. Genomic hotspots of fusion genes, differences between subtypes and small number of recurrent fusions are the most relevant characteristics of these events in breast cancer. Further investigation is necessary to comprehend the biological significance of these fusions.

Keywords: RNA-seq; breast cancer; gene-fusion; next-generation sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / classification
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Chromosomes, Human, Pair 17
  • Chromosomes, Human, Pair 20
  • Chromosomes, Human, Pair 8
  • DNA Copy Number Variations
  • Estrogen Receptor alpha / genetics
  • Female
  • Gene Fusion*
  • Genes, erbB-2
  • Genome, Human*
  • Humans
  • Polymorphism, Single Nucleotide


  • ESR1 protein, human
  • Estrogen Receptor alpha