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RhoGAP domain-containing fusions and PPAPDC1A fusions are recurrent and prognostic in diffuse gastric cancer

Author

Listed:
  • Hanna Yang

    (National Cancer Center)

  • Dongwan Hong

    (National Cancer Center)

  • Soo Young Cho

    (National Cancer Center)

  • Young Soo Park

    (University of Ulsan College of Medicine)

  • Woo Ri Ko

    (National Cancer Center)

  • Ju Hee Kim

    (National Cancer Center)

  • Hoon Hur

    (Ajou University School of Medicine)

  • Jongkeun Lee

    (National Cancer Center)

  • Su-Jin Kim

    (Dong-A University College of Medicine)

  • Sun Young Kwon

    (Keimyung University School of Medicine)

  • Jae-Hyuk Lee

    (Chonnam National University Medical School)

  • Do Youn Park

    (Pusan National University Hospital and Pusan National University School of Medicine)

  • Kyu Sang Song

    (Chungnam National University)

  • Heekyung Chang

    (Kosin University College of Medicine)

  • Min-Hee Ryu

    (University of Ulsan College of Medicine)

  • Kye Soo Cho

    (National Cancer Center)

  • Jeong Won Kang

    (National Cancer Center)

  • Myeong-Cherl Kook

    (National Cancer Center)

  • Nina Thiessen

    (British Columbia Cancer Agency)

  • An He

    (British Columbia Cancer Agency)

  • Andy Mungall

    (British Columbia Cancer Agency)

  • Sang-Uk Han

    (Ajou University School of Medicine)

  • Hark Kyun Kim

    (National Cancer Center
    National Cancer Center Graduate School of Cancer Science and Policy)

Abstract

We conducted an RNA sequencing study to identify novel gene fusions in 80 discovery dataset tumors collected from young patients with diffuse gastric cancer (DGC). Twenty-five in-frame fusions are associated with DGC, three of which (CLDN18-ARHGAP26, CTNND1-ARHGAP26, and ANXA2-MYO9A) are recurrent in 384 DGCs based on RT-PCR. All three fusions contain a RhoGAP domain in their 3’ partner genes. Patients with one of these three fusions have a significantly worse prognosis than those without. Ectopic expression of CLDN18-ARHGAP26 promotes the migration and invasion capacities of DGC cells. Parallel targeted RNA sequencing analysis additionally identifies TACC2-PPAPDC1A as a recurrent and poor prognostic in-frame fusion. Overall, PPAPDC1A fusions and in-frame fusions containing a RhoGAP domain clearly define the aggressive subset (7.5%) of DGCs, and their prognostic impact is greater than, and independent of, chromosomal instability and CDH1 mutations. Our study may provide novel genomic insights guiding future strategies for managing DGCs.

Suggested Citation

  • Hanna Yang & Dongwan Hong & Soo Young Cho & Young Soo Park & Woo Ri Ko & Ju Hee Kim & Hoon Hur & Jongkeun Lee & Su-Jin Kim & Sun Young Kwon & Jae-Hyuk Lee & Do Youn Park & Kyu Sang Song & Heekyung Cha, 2018. "RhoGAP domain-containing fusions and PPAPDC1A fusions are recurrent and prognostic in diffuse gastric cancer," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06747-4
    DOI: 10.1038/s41467-018-06747-4
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