Recurrent fusion transcripts detected by whole‐transcriptome sequencing of 120 primary breast cancer samples. Issue 11 (30th July 2015)

• Record Type: Journal Article
• Authors: Kim, Jisun; Kim, Sehwan; Ko, Seyoon; In, Yong‐ho; Moon, Hyeong‐Gon; Ahn, Soo Kyung; Kim, Min Kyoon; Lee, Minju; Hwang, Jin‐Ha; Ju, Young Seok; Kim, Jong‐Il; Noh, Dong‐Young; Kim, Sun; Park, Jung‐Hoon; Rhee, Hwanseok; Kim, Sunghoon; Han, Wonshik
• Is Part Of: Genes, chromosomes & cancer. Volume 54:Issue 11(2015:Nov.)
• Page Start: 681
• Page End: 691
• Publication Date: 2015-07-30
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22279
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 (<italic>P</italic> < 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 (<italic>PRDX1‐AKR1A1, TACSTD2‐OMA1</italic>, and <italic>C2CD2‐TFF1</italic>) and three were off‐frame (<italic>CEACAM7‐CEACAM6, CYP4X1‐CYP4Z2P</italic>, and <italic>EEF1DP3‐FRY</italic>). Notably, the novel read‐through fusion, <italic>EEF1DP3‐FRY</italic>, was identified and validated in 6.7% (8/120) of the breast cancer samples. This off‐frame fusion results in early truncation of the <italic>FRY</italic> gene, which plays a key role in the structural integrity during mitosis. Three previously reported fusions, <italic>PPP1R1B‐STARD3, MFGE8‐HAPL</italic>, and <italic>ETV6‐NTRK3</italic>, were detected in 8.3, 3.3, and 0.8% of the 120 samples, respectively, by both deFuse and Chimerascan. The recently reported <italic>MAGI3‐AKT3</italic> 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. © 2015 Wiley Periodicals, Inc.</p> </abstract>