Abstract
PurposeFusion 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.MethodsRNA-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.ResultsA 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.ConclusionsIn 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.
Highlights
Breast cancer is the most frequently diagnosed female cancer in the United States with a lifetime risk of 12% and an expected number of 268,600 new cases and 41,760 deaths1 3 Vol.:(0123456789)Journal of Cancer Research and Clinical Oncology (2020) 146:503–514 in 2019 (American Cancer Society 2019a)
We investigate the fusion gene landscape in the transcriptome of 18 Triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSOC) patients who were treated with buparlisib and olaparib in the aforementioned phase I trial using RNA sequencing
Progression-free survival (PFS) was measured at a mean of 10.2 ± 1.9 (± standard error of the mean (SEM)) months for TNBC patients and at a mean of 18.2 ± 6.9 (± SEM) months for HGSOC patients
Summary
Breast cancer is the most frequently diagnosed female cancer in the United States with a lifetime risk of 12% and an expected number of 268,600 new cases and 41,760 deaths1 3 Vol.:(0123456789)Journal of Cancer Research and Clinical Oncology (2020) 146:503–514 in 2019 (American Cancer Society 2019a). Breast cancer is the most frequently diagnosed female cancer in the United States with a lifetime risk of 12% and an expected number of 268,600 new cases and 41,760 deaths. Since TNBC patients do not respond to hormonal treatment or HER2-directed therapy, treatment options are restricted to chemotherapy such as platinum/taxane or alkylating agents. Ovarian cancer represents the fifth most frequently diagnosed female cancer in the United States with a lifetime risk of 1.3% and an estimated number of 22,530 new cases and 13,980 deaths in 2019 (American Cancer Society 2019b). Standard treatment for HGSOC consists of surgery followed by platinum/taxane chemotherapy. Despite these measures, the prognosis remains grim. The prognosis remains grim. 25% of HGSOC recur within the first 6 months after treatment and a 5-year overall survival (OS) of 31% has been reported (Jemal et al 2009)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
