AUTHOR=Li Juanni , Hu Kuan , Huang Jinzhou , Zhou Lei , Yan Yuanliang , Xu Zhijie 

TITLE=A Pancancer Analysis of the Expression Landscape and Clinical Relevance of Fibroblast Growth Factor Receptor 2 in Human Cancers

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.644854

DOI=10.3389/fonc.2021.644854

ISSN=2234-943X

ABSTRACT=<p><bold>Background:</bold> Fibroblast growth factor receptor 2 (FGFR2) is frequently altered in tumors and one of the top therapeutic targets in cholangiocarcinoma (CHOL) with <italic>FGFR2</italic> fusions. Although there have been several studies on individual tumors, a comprehensive analysis of <italic>FGFR2</italic> genetic aberrations and their simultaneous clinical implications across different tumors have not been reported.</p><p><bold>Methods:</bold> In this study, we used the large comprehensive datasets available, covering over 10,000 tumor samples across more than 30 cancer types, to analyze <italic>FGFR2</italic> abnormal expression, methylation, alteration (mutations/fusions and amplification/deletion), and their clinical associations.</p><p><bold>Results:</bold> Alteration frequency, mutation location distribution, oncogenic effects, and therapeutic implications varied among different cancers. The overall mutation rate of <italic>FGFR2</italic> is low in pancancer. CHOL had the highest mutation frequency, and fusion accounted for the major proportion. All these fusion aberrations in CHOL were targetable, and an FDA-approved drug was approved recently. Uterine corpus endometrial carcinoma (UCEC) had the highest number of <italic>FGFR2</italic> mutations, and the most frequently mutated positions were S252W and N549K, where the functional impact was oncogenic, but targeted therapy was less effective. Additionally, DNA methylation was associated with <italic>FGFR2</italic> expression in several cancers. Moreover, FGFG2 expression and genetic aberrations showed clinical associations with patient survival in several cancers, indicating their potential for application as new tumor markers and therapeutic targets.</p><p><bold>Conclusions:</bold> This study showed the full <italic>FGFR2</italic> alteration spectrum and provided a broad molecular perspective of <italic>FGFR2</italic> in a comprehensive manner, suggesting some new directions for clinical targeted therapy of cancers.</p>