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Integrated Analysis of Structural Variation and RNA Expression of FGFR2 and Its Splicing Modulator ESRP1 Highlight the ESRP1amp-FGFR2norm-FGFR2-IIIchigh Axis in Diffuse Gastric Cancer

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Ipatimup—Institute of Molecular Pathology and Immunology, University of Porto, Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal
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i3S—Instituto de Investigação e Inovação em Saúde, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal
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Master in Oncology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), 4050-313 Porto, Portugal
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Department of Computer Science, Faculty of Sciences, University of Porto, Rua Campo Alegre 1021/1055, 4169-007 Porto, Portugal
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Department Pathology and Oncology Faculty of Medicine University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
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Author to whom correspondence should be addressed.
Cancers 2020, 12(1), 70; https://doi.org/10.3390/cancers12010070
Received: 15 November 2019 / Revised: 15 December 2019 / Accepted: 23 December 2019 / Published: 25 December 2019
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 FGFR2 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 FGFR2 and its splicing regulator ESRP1 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 FGFR2/ESRP1 across several cohorts. We discovered that both genes were frequently amplified and demethylated in GC, resulting in increased ESRP1 expression and of a specific FGFR2 isoform: FGFR2-IIIb. We also showed that ESRP1 amplification in GC correlated with a significant decreased expression of FGFR2-IIIc, an alternative FGFR2 splicing isoform. Furthermore, when we performed a survival analysis, we observed that patients harboring diffuse-type tumors with low FGFR2-IIIc expression revealed a better overall survival than patients with FGFR2-IIIc high-expressing diffuse tumors. Our results encourage further studies on the role of ESRP1 in GC and support FGFR2-IIIc as a relevant biomarker in GC. View Full-Text
Keywords: gastric cancer; FGFR2; FGFR2-IIIb; FGFR2-IIIc; ESRP1; diffuse gastric cancer; FGFR2; FGFR2-IIIb; FGFR2-IIIc; ESRP1; diffuse
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MDPI and ACS Style

Teles, S.P.; Oliveira, P.; Ferreira, M.; Carvalho, J.; Ferreira, P.; Oliveira, C. Integrated Analysis of Structural Variation and RNA Expression of FGFR2 and Its Splicing Modulator ESRP1 Highlight the ESRP1amp-FGFR2norm-FGFR2-IIIchigh Axis in Diffuse Gastric Cancer. Cancers 2020, 12, 70. https://doi.org/10.3390/cancers12010070

AMA Style

Teles SP, Oliveira P, Ferreira M, Carvalho J, Ferreira P, Oliveira C. Integrated Analysis of Structural Variation and RNA Expression of FGFR2 and Its Splicing Modulator ESRP1 Highlight the ESRP1amp-FGFR2norm-FGFR2-IIIchigh Axis in Diffuse Gastric Cancer. Cancers. 2020; 12(1):70. https://doi.org/10.3390/cancers12010070

Chicago/Turabian Style

Teles, Sara P., Patrícia Oliveira, Marta Ferreira, Joana Carvalho, Pedro Ferreira, and Carla Oliveira. 2020. "Integrated Analysis of Structural Variation and RNA Expression of FGFR2 and Its Splicing Modulator ESRP1 Highlight the ESRP1amp-FGFR2norm-FGFR2-IIIchigh Axis in Diffuse Gastric Cancer" Cancers 12, no. 1: 70. https://doi.org/10.3390/cancers12010070

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