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PPP1R1B-STARD3 chimeric fusion transcript in human gastric cancer promotes tumorigenesis through activation of PI3K/AKT signaling

Oncogene volume 33, pages 5341–5347 (2014)Cite this article

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Abstract

Fusion genes act as potent oncogenes, resulting from chromosomal rearrangements or abnormal transcription in many human cancers. Although multiple gastric cancer genomes have been sequenced, the driving recurrent gene fusions have not been well characterized. Here, we used paired-end transcriptome sequencing to identify novel gene fusions in 18 human gastric cancer cell lines and 18 pairs of primary human gastric cancer tissues and their adjacent normal tissues. Multiple samples revealed expression of PPP1R1B-STARD3 fusion transcript. The presence of PPP1R1B-STARD3 correlated with elevated levels of PPP1R1B mRNA. PPP1R1B-STARD3 fusion transcript was detected in 21.3% of primary human gastric cancers but not in adjacent matched normal gastric tissues. Based on reverse transcription PCR analysis of DNA, unlike other fusions described in gastric cancer, the PPP1R1B-STARD3 appears to be generated by RNA processing without chromosomal rearrangement. Overexpression of PPP1R1B-STARD3 in MKN-28 significantly increased cell proliferation and colony formation. This increased proliferation was mediated by activation of phosphatidylinositol-3-kinase (PI3K)/AKT signaling. Furthermore, expression of PPP1R1B-STARD3 fusion transcript enhanced the tumor growth of MKN-28 cells in athymic nude mice. These findings show that PPP1R1B-STARD3 fusion transcript has a key role in subsets of gastric cancers through the activation of PI3K/AKT signaling.

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Acknowledgements

This work was supported in part by the National Research Foundation of Korea (NRF) grants (2009-0081756 and 2012M3A9C4048736 to S-JK). JB and SL were supported by TheragenEtex and Genome Research Foundation internal funds. JB was supported by the Industrial Strategic Technology Development Program (10040231) funded by the Ministry of Knowledge Economy (MKE, Korea).

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Author notes

  1. S M Yun, K Yoon, S Lee and E Kim: These authors contributed equally to this work.

Authors and Affiliations

  1. CHA Cancer Institute, CHA University, Seoul, Korea

    S M Yun, K Yoon, E Kim, J Choe, J M Kang, P Kim, Y Choi, H Yoo & S-J Kim

  2. Department of Biomedical Science, College of Life Science, CHA University, 605 Yeoksam-dong, Gangnam-gu, Seoul, Korea

    S M Yun & S-J Kim

  3. Personal Genomics Institute, Genome Research Foundation, Suwon, Korea

    S Lee, S Jho & J Bhak

  4. TheragenEtex Bio Institute, TheragenEtex Inc., Suwon, Korea

    S Lee & J Bhak

  5. Cancer Research Institute, Seoul National University, Seoul, Korea

    S-H Kong, T-S Han & H-K Yang

  6. Department of Surgery, Seoul National University College of Medicine, Seoul, Korea

    S-H Kong & H-K Yang

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  1. S M Yun
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Correspondence to S-J Kim.

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The authors declare competing financial interests. Some authors are present employees of TheragenEtex, and some of them have personal financial interests as shareholders in TheragenEtex.

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Author Contributions

SMY and KY performed research, analyzed data and wrote the manuscript; SL analyzed and interpreted sequencing data; EK and PK performed research and collected data; JMK performed an animal study; JC, YC and HY contributed to the manuscript; T-SH, S-HK and H-KY collected clinical information and prepared clinical samples; SJ and JB analyzed and collected sequencing data; S-JK designed research, interpreted data and drafted the manuscript.

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Yun, S., Yoon, K., Lee, S. et al. PPP1R1B-STARD3 chimeric fusion transcript in human gastric cancer promotes tumorigenesis through activation of PI3K/AKT signaling. Oncogene 33, 5341–5347 (2014). https://doi.org/10.1038/onc.2013.472

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