Recurrent fusion transcripts detected by whole-transcriptome sequencing of 120 primary breast cancer samples

Jisun Kim, Sehwan Kim, Seyoon Ko, Yong ho In, Hyeong Gon Moon, Soo Kyung Ahn, Min Kyoon Kim, Minju Lee, Jin Ha Hwang, Young Seok Ju, Jong Il Kim, Dong Young Noh, Sun Kim, Jung Hoon Park, Hwanseok Rhee, Sunghoon Kim, Wonshik Han

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15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)681-691
Number of pages11
JournalGenes Chromosomes and Cancer
Volume54
Issue number11
DOIs
Publication statusPublished - 2015 Nov 1

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cancer Research

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    Kim, J., Kim, S., Ko, S., In, Y. H., Moon, H. G., Ahn, S. K., Kim, M. K., Lee, M., Hwang, J. H., Ju, Y. S., Kim, J. I., Noh, D. Y., Kim, S., Park, J. H., Rhee, H., Kim, S., & Han, W. (2015). Recurrent fusion transcripts detected by whole-transcriptome sequencing of 120 primary breast cancer samples. Genes Chromosomes and Cancer, 54(11), 681-691. https://doi.org/10.1002/gcc.22279