Functional Distinctions of Endometrial Cancer-Associated Mutations in the Fibroblast Growth Factor Receptor 2 Gene
Functional analysis of somatic mutations in tumorigenesis facilitates the development and optimization of personalized therapy for cancer patients. The <i>fibroblast growth factor receptor 2</i> (<i>FGFR2</i>) gene is frequently mutated in endometrial cancer (EC), but the fun...
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MDPI AG
2023-09-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/18/2227 |
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| author | Garima Dixit Benjamin A. Pappas Gourav Bhardwaj Willow Schanz Thorsten Maretzky |
| author_facet | Garima Dixit Benjamin A. Pappas Gourav Bhardwaj Willow Schanz Thorsten Maretzky |
| author_sort | Garima Dixit |
| collection | DOAJ |
| description | Functional analysis of somatic mutations in tumorigenesis facilitates the development and optimization of personalized therapy for cancer patients. The <i>fibroblast growth factor receptor 2</i> (<i>FGFR2</i>) gene is frequently mutated in endometrial cancer (EC), but the functional implications of <i>FGFR2</i> mutations in cancer development remain largely unexplored. In this study, we introduced a reliable and readily deployable screening method to investigate the effects of <i>FGFR2</i> mutations. We demonstrated that distinct mutations in <i>FGFR2</i> can lead to differential downstream consequences, specifically affecting a disintegrin- and metalloprotease 17 (ADAM17)-dependent shedding of the epidermal growth factor receptor (EGFR) ligand heparin-binding EGF-like growth factor (HB-EGF) and phosphorylation of mitogen-activated protein kinases (MAPKs). Furthermore, we showed that the distribution of mutations within the <i>FGFR2</i> gene can influence their oncogenic effects. Together, these findings provide important insights into the complex nature of <i>FGFR2</i> mutations and their potential implications for EC. By unraveling the distinct effects of different mutations, our study contributes to the identification of personalized treatment strategies for patients with <i>FGFR2</i>-mutated cancers. This knowledge has the potential to guide the development of targeted therapies that specifically address the underlying molecular alterations associated with <i>FGFR2</i> mutations, ultimately improving patient outcomes in EC and potentially other cancer types characterized by <i>FGFR2</i> mutations. |
| first_indexed | 2024-03-10T22:56:18Z |
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| id | doaj.art-74b0a621ffb04cfa8e64e15f545f4c39 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T22:56:18Z |
| publishDate | 2023-09-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-74b0a621ffb04cfa8e64e15f545f4c392023-11-19T09:59:06ZengMDPI AGCells2073-44092023-09-011218222710.3390/cells12182227Functional Distinctions of Endometrial Cancer-Associated Mutations in the Fibroblast Growth Factor Receptor 2 GeneGarima Dixit0Benjamin A. Pappas1Gourav Bhardwaj2Willow Schanz3Thorsten Maretzky4Inflammation Program and Division of Infectious Diseases, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAInflammation Program and Division of Infectious Diseases, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAFraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAInflammation Program and Division of Infectious Diseases, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAInflammation Program and Division of Infectious Diseases, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAFunctional analysis of somatic mutations in tumorigenesis facilitates the development and optimization of personalized therapy for cancer patients. The <i>fibroblast growth factor receptor 2</i> (<i>FGFR2</i>) gene is frequently mutated in endometrial cancer (EC), but the functional implications of <i>FGFR2</i> mutations in cancer development remain largely unexplored. In this study, we introduced a reliable and readily deployable screening method to investigate the effects of <i>FGFR2</i> mutations. We demonstrated that distinct mutations in <i>FGFR2</i> can lead to differential downstream consequences, specifically affecting a disintegrin- and metalloprotease 17 (ADAM17)-dependent shedding of the epidermal growth factor receptor (EGFR) ligand heparin-binding EGF-like growth factor (HB-EGF) and phosphorylation of mitogen-activated protein kinases (MAPKs). Furthermore, we showed that the distribution of mutations within the <i>FGFR2</i> gene can influence their oncogenic effects. Together, these findings provide important insights into the complex nature of <i>FGFR2</i> mutations and their potential implications for EC. By unraveling the distinct effects of different mutations, our study contributes to the identification of personalized treatment strategies for patients with <i>FGFR2</i>-mutated cancers. This knowledge has the potential to guide the development of targeted therapies that specifically address the underlying molecular alterations associated with <i>FGFR2</i> mutations, ultimately improving patient outcomes in EC and potentially other cancer types characterized by <i>FGFR2</i> mutations.https://www.mdpi.com/2073-4409/12/18/2227a disintegrin and metalloprotease 17 (ADAM17)fibroblast growth factor receptor 2 (FGFR2)epidermal growth factor receptor (EGFR)heparin-binding EGF-like growth factor (HB-EGF)endometrial cancer (EC) |
| spellingShingle | Garima Dixit Benjamin A. Pappas Gourav Bhardwaj Willow Schanz Thorsten Maretzky Functional Distinctions of Endometrial Cancer-Associated Mutations in the Fibroblast Growth Factor Receptor 2 Gene Cells a disintegrin and metalloprotease 17 (ADAM17) fibroblast growth factor receptor 2 (FGFR2) epidermal growth factor receptor (EGFR) heparin-binding EGF-like growth factor (HB-EGF) endometrial cancer (EC) |
| title | Functional Distinctions of Endometrial Cancer-Associated Mutations in the Fibroblast Growth Factor Receptor 2 Gene |
| title_full | Functional Distinctions of Endometrial Cancer-Associated Mutations in the Fibroblast Growth Factor Receptor 2 Gene |
| title_fullStr | Functional Distinctions of Endometrial Cancer-Associated Mutations in the Fibroblast Growth Factor Receptor 2 Gene |
| title_full_unstemmed | Functional Distinctions of Endometrial Cancer-Associated Mutations in the Fibroblast Growth Factor Receptor 2 Gene |
| title_short | Functional Distinctions of Endometrial Cancer-Associated Mutations in the Fibroblast Growth Factor Receptor 2 Gene |
| title_sort | functional distinctions of endometrial cancer associated mutations in the fibroblast growth factor receptor 2 gene |
| topic | a disintegrin and metalloprotease 17 (ADAM17) fibroblast growth factor receptor 2 (FGFR2) epidermal growth factor receptor (EGFR) heparin-binding EGF-like growth factor (HB-EGF) endometrial cancer (EC) |
| url | https://www.mdpi.com/2073-4409/12/18/2227 |
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