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Nat Commun. 2018 Oct 25;9(1):4439. doi: 10.1038/s41467-018-06747-4.

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

Author information

1
National Cancer Center, Goyang, Gyeonggi, 10408, Republic of Korea.
2
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
3
Department of Surgery, Ajou University School of Medicine, Suwon, 443-380, Republic of Korea.
4
Department of Pathology, Dong-A University College of Medicine, Busan, 602-812, Republic of Korea.
5
Department of Pathology, Keimyung University School of Medicine, Daegu, 41931, Republic of Korea.
6
Department of Pathology, Chonnam National University Medical School, Gwangju, 501-746, Republic of Korea.
7
Department of Pathology and BioMedical Research Institute, Pusan National University Hospital and Pusan National University School of Medicine, Busan, 602-739, Republic of Korea.
8
Department of Pathology, School of Medicine, Chungnam National University, Daejeon, 301-747, Republic of Korea.
9
Department of Pathology, Kosin University College of Medicine, Busan, 49267, Republic of Korea.
10
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Republic of Korea.
11
British Columbia Cancer Agency, Vancouver, BC, V5Z 1L3, Canada.
12
National Cancer Center, Goyang, Gyeonggi, 10408, Republic of Korea. hkim@ncc.re.kr.
13
National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Gyeonggi, 10408, Republic of Korea. hkim@ncc.re.kr.

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.

PMID:
30361512
PMCID:
PMC6202325
DOI:
10.1038/s41467-018-06747-4
[Indexed for MEDLINE]
Free PMC Article

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