Recurrent and pathological gene fusions in breast cancer: current advances in genomic discovery and clinical implications

Breast Cancer Res Treat. 2016 Jul;158(2):219-32. doi: 10.1007/s10549-016-3876-y. Epub 2016 Jul 2.


Gene fusions have long been considered principally as the oncogenic events of hematologic malignancies, but have recently gained wide attention in solid tumors due to several milestone discoveries and the advancement of deep sequencing technologies. With the progress in deep sequencing studies of breast cancer transcriptomes and genomes, the discovery of recurrent and pathological gene fusions in breast cancer is on the focus. Recently, driven by new deep sequencing studies, several recurrent or pathological gene fusions have been identified in breast cancer, including ESR1-CCDC170, SEC16A-NOTCH1, SEC22B-NOTCH2, and ESR1-YAP1 etc. More important, most of these gene fusions are preferentially identified in the more aggressive breast cancers, such as luminal B, basal-like, or endocrine-resistant breast cancer, suggesting recurrent gene fusions as additional key driver events in these tumors other than the known drivers such as the estrogen receptor. In this paper, we have comprehensively summarized the newly identified recurrent or pathological gene fusion events in breast cancer, reviewed the contributions of new genomic and deep sequencing technologies to new fusion discovery and the integrative bioinformatics tools to analyze these data, highlighted the biological relevance and clinical implications of these fusion discoveries, and discussed future directions of gene fusion research in breast cancer.

Keywords: Bioinformatics; Breast cancer; Genomics; Next-generation sequencing; Recurrent gene fusions; Tumorigenesis.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Female
  • Gene Expression Profiling
  • Gene Fusion*
  • Genetic Predisposition to Disease
  • Genomics / methods*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Sequence Analysis, DNA