Integrated Analysis of Structural Variation and RNA Expression of FGFR2 and Its Splicing Modulator ESRP1 Highlight the -- Axis in Diffuse Gastric Cancer.

Gastric Cancer (GC) is one of the most common and deadliest types of cancer in the world. To improve GC prognosis, increasing efforts are being made to develop new targeted therapies. Although genetic amplification and protein overexpression in GC have been targeted in clinical trials, so far no improvement in patient overall survival has been found. To address this issue, we studied genetic and epigenetic events affecting and its splicing regulator in GC that could be used as new therapeutic targets or predictive biomarkers. We performed copy number variation (CNV), DNA methylation, and RNA expression analyses of / across several cohorts. We discovered that both genes were frequently amplified and demethylated in GC, resulting in increased expression and of a specific isoform: . We also showed that amplification in GC correlated with a significant decreased expression of , an alternative splicing isoform. Furthermore, when we performed a survival analysis, we observed that patients harboring diffuse-type tumors with low expression revealed a better overall survival than patients with high-expressing diffuse tumors. Our results encourage further studies on the role of in GC and support as a relevant biomarker in GC.