Transcriptome analysis reveals overlap in fusion genes in a phase I clinical cohort of TNBC and HGSOC patients treated with buparlisib and olaparib

J Cancer Res Clin Oncol. 2020 Feb;146(2):503-514. doi: 10.1007/s00432-019-03078-9. Epub 2019 Nov 19.


Purpose: Fusion genes can be therapeutically relevant if they result in constitutive activation of oncogenes or repression of tumor suppressors. However, the prevalence and role of fusion genes in female cancers remain largely unexplored. Here, we investigate the fusion gene landscape in triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSOC), two subtypes of female cancers with high molecular similarity but limited treatment options at present.

Methods: RNA-seq was utilized to identify fusion genes in a cohort of 18 TNBC and HGSOC patients treated with the PI3K inhibitor buparlisib and the PARP inhibitor olaparib in a phase I clinical trial (NCT01623349). Differential gene expression analysis was performed to assess the function of fusion genes in silico. Finally, these findings were correlated with the reported clinical outcomes.

Results: A total of 156 fusion genes was detected, whereof 44/156 (28%) events occurred in more than one patient. Low recurrence across samples indicated that the majority of fusion genes were private passenger events. The long non-coding RNA MALAT1 was involved in 97/156 (62%) fusion genes, followed in prevalence by MUC16, FOXP1, WWOX and XIST. Gene expression of FOXP1 was significantly elevated in patients with vs. without FOXP1 fusion (P= 0.02). From a clinical perspective, FOXP1 fusions were associated with a favorable overall survival.

Conclusions: In summary, this study provides the first characterization of fusion genes in a cohort of TNBC and HGSOC patients. An improved mechanistic understanding of fusion genes will support the future identification of innovative therapeutic approaches for these challenging diseases.

Keywords: Breast cancer; Fusion gene; Genomic profiling; Ovarian cancer; RNA-seq.

MeSH terms

  • Adult
  • Aged
  • Aminopyridines / administration & dosage
  • Aminopyridines / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Clinical Trials, Phase I as Topic
  • Cystadenocarcinoma, Serous / drug therapy
  • Cystadenocarcinoma, Serous / genetics*
  • Female
  • Forkhead Transcription Factors / genetics
  • Gene Expression Profiling
  • Gene Fusion*
  • Humans
  • Middle Aged
  • Morpholines / administration & dosage
  • Morpholines / adverse effects
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics*
  • Phthalazines / administration & dosage
  • Phthalazines / adverse effects
  • Piperazines / administration & dosage
  • Piperazines / adverse effects
  • RNA-Seq / methods
  • Repressor Proteins / genetics
  • Triple Negative Breast Neoplasms / drug therapy
  • Triple Negative Breast Neoplasms / genetics*


  • Aminopyridines
  • FOXP1 protein, human
  • Forkhead Transcription Factors
  • Morpholines
  • NVP-BKM120
  • Phthalazines
  • Piperazines
  • Repressor Proteins
  • olaparib