Abstract 1680: RhoGAP and PAP2 domain-containing fusions are recurrent and prognostic in gastric cancer

Abstract We conducted an RNA sequencing study to identify novel in-frame gene fusions in 80 discovery dataset tumors collected from young Korean patients with diffuse gastric cancer. Twenty-five in-frame fusions were associated with diffuse gastric cancer, three of which (CLDN18-ARHGAP26, CTNND1-ARHGAP26, and ANXA2-MYO9A) were recurrent in 384 diffuse gastric cancers based on RT-PCR. All three fusions contained a RhoGAP domain in their 3’ partner genes. Patients with one of these three RhoGAP domain fusions had a significantly worse prognosis than those without such fusions. The median survival was 29.1 [95% CI, 5.7–not reached] and 94.6 [95% CI, 62.0–not reached] months, respectively (P=0.011, log-rank; HR, 2.8 [95% CI, 1.5–5.3]). Ectopic expression of CLDN18-ARHGAP26 promoted the migration and invasion capacities of diffuse gastric cancer cells. Parallel targeted RNA sequencing analysis additionally identified PAP2 domain-containing fusions as recurrent and poor prognostic in-frame fusions. Overall, in-frame gene fusions containing either RhoGAP or PAP2 domain clearly defined the aggressive subset (7.5%) of diffuse gastric cancer, and their prognostic impact (HR, 3.4 [95% CI, 2.0–5.7]) was greater than, and independent of, chromosomal instability and CDH1mutations. Our study may provide novel genomic insights guiding future strategies for managing diffuse gastric cancer. Citation Format: Hark K. Kim. RhoGAP and PAP2 domain-containing fusions are recurrent and prognostic in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1680.