title: Recurrent fusion transcripts detected by whole-transcriptome sequencing of 120 primary breast cancer samples.
abstract: Relatively few recurrent gene fusion events have been associated with breast cancer to date. In an effort to uncover novel fusion transcripts, we performed whole-transcriptome sequencing of 120 fresh-frozen primary breast cancer samples and five adjacent normal breast tissues using the Illumina HiSeq2000 platform. Three different fusion-detecting tools (deFuse, Chimerascan, and TopHatFusion) were used, and the results were compared. These tools detected 3,831, 6,630 and 516 fusion transcripts (FTs) overall. We primarily focused on the results obtained using the deFuse software. More FTs were identified from HER2 subtype breast cancer samples than from the luminal or triple-negative subtypes (P < 0.05). Seventy fusion candidates were selected for validation, and 32 (45.7%) were confirmed by RT-PCR and Sanger sequencing. Of the validated fusions, six were recurrent (found in 2 or more samples), three were in-frame (PRDX1-AKR1A1, TACSTD2-OMA1, and C2CD2-TFF1) and three were off-frame (CEACAM7-CEACAM6, CYP4X1-CYP4Z2P, and EEF1DP3-FRY). Notably, the novel read-through fusion, EEF1DP3-FRY, was identified and validated in 6.7% (8/120) of the breast cancer samples. This off-frame fusion results in early truncation of the FRY gene, which plays a key role in the structural integrity during mitosis. Three previously reported fusions, PPP1R1B-STARD3, MFGE8-HAPL, and ETV6-NTRK3, were detected in 8.3, 3.3, and 0.8% of the 120 samples, respectively, by both deFuse and Chimerascan. The recently reported MAGI3-AKT3 fusion was not detected in our analysis. Although future work will be needed to examine the biological significance of our new findings, we identified a number of novel fusions and confirmed some previously reported fusions.
authors.affiliation: Department of Surgery, Asan Medical Center, Seoul, Korea.
authors.forename: Jisun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Macrogen Inc., Seoul, Korea.
authors.forename: Sehwan
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Statistics, Seoul National University, Seoul, Korea.
authors.forename: Seyoon
authors.initials: S
authors.lastname: Ko
authors.affiliation: Medicinal Bioconvergence Research Center, Seoul, Korea.
authors.forename: Yong-ho
authors.initials: YH
authors.lastname: In
authors.affiliation: Department of Surgery, Seoul National University Hospital, Seoul, Korea.|Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: Hyeong-Gon
authors.initials: HG
authors.lastname: Moon
authors.affiliation: Department of Surgery, Seoul National University Hospital, Seoul, Korea.
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Ahn
authors.affiliation: Department of Surgery, Seoul National University Hospital, Seoul, Korea.
authors.forename: Min Kyoon
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: Minju
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Biomedical Science, Seoul National University Graduate School, Seoul, Korea.
authors.forename: Jin-Ha
authors.initials: JH
authors.lastname: Hwang
authors.affiliation: Macrogen Inc., Seoul, Korea.|Genomic Medicine Institute(GMI), Medical Research Center, Seoul National University, Seoul, Korea.
authors.forename: Young Seok
authors.initials: YS
authors.lastname: Ju
authors.affiliation: Department of Biomedical Science, Seoul National University Graduate School, Seoul, Korea.|Genomic Medicine Institute(GMI), Medical Research Center, Seoul National University, Seoul, Korea.|Department of Biochemistry, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Department of Surgery, Seoul National University Hospital, Seoul, Korea.|Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
authors.affiliation: Department of Statistics, Seoul National University, Seoul, Korea.
authors.forename: Sun
authors.initials: S
authors.lastname: Kim
authors.affiliation: Macrogen Inc., Seoul, Korea.
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Park
authors.affiliation: Macrogen Inc., Seoul, Korea.
authors.forename: Hwanseok
authors.initials: H
authors.lastname: Rhee
authors.affiliation: Medicinal Bioconvergence Research Center, Seoul, Korea.|Medicinal Bioconvergence Research Center, Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, College of Pharmacy, Seoul National University, Seoul, Korea.
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Surgery, Seoul National University Hospital, Seoul, Korea.|Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: Wonshik
authors.initials: W
authors.lastname: Han
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D050939:Gene Fusion; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D017423:Sequence Analysis, RNA / Q000379:methods; D012984:Software; D059467:Transcriptome
chemical_list: D012333:RNA, Messenger