Lack of Targetable FGFR2 Fusions in Endemic Fluke-Associated Cholangiocarcinoma
PURPOSE Cholangiocarcinoma (CCA) remains a disease with poor prognosis and limited therapeutic options. Identification of driver genetic alterations may lead to the discovery of more effective targeted therapies. CCAs harboring FGFR2 fusions have recently demonstrated promising responses to FGFR inh...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society of Clinical Oncology
2020-11-01
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| Series: | JCO Global Oncology |
| Online Access: | https://ascopubs.org/doi/10.1200/GO.20.00030 |
| _version_ | 1818357863342407680 |
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| author | Sarinya Kongpetch Apinya Jusakul Jing Quan Lim Cedric Chuan Young Ng Jason Yongsheng Chan Vikneswari Rajasegaran Tse Hui Lim Kiat Hon Lim Su Pin Choo Simona Dima Irinel Popescu Dan G. Duda Veerapol Kukongviriyapan Narong Khuntikeo Chawalit Pairojkul Steven G. Rozen Patrick Tan Bin Tean Teh |
| author_facet | Sarinya Kongpetch Apinya Jusakul Jing Quan Lim Cedric Chuan Young Ng Jason Yongsheng Chan Vikneswari Rajasegaran Tse Hui Lim Kiat Hon Lim Su Pin Choo Simona Dima Irinel Popescu Dan G. Duda Veerapol Kukongviriyapan Narong Khuntikeo Chawalit Pairojkul Steven G. Rozen Patrick Tan Bin Tean Teh |
| author_sort | Sarinya Kongpetch |
| collection | DOAJ |
| description | PURPOSE Cholangiocarcinoma (CCA) remains a disease with poor prognosis and limited therapeutic options. Identification of driver genetic alterations may lead to the discovery of more effective targeted therapies. CCAs harboring FGFR2 fusions have recently demonstrated promising responses to FGFR inhibitors, highlighting their potential relevance as predictive biomarkers. CCA incidence is high in the northeast of Thailand and its neighboring countries because of chronic infection with the liver fluke Opisthorchis viverrini (Ov). However, there are currently no available data on the prevalence of FGFR alterations in fluke-associated CCA in endemic countries. MATERIALS AND METHODS In this study, we performed anchored multiplex polymerase chain reaction target enrichment RNA sequencing of FGFR1-3, validated by fluorescence in situ hybridization and Sanger sequencing, in 121 Ov-associated and 95 non–Ov-associated CCA tumors. RESULTS Compared with non–fluke-associated CCA (11/95; 11.6%), FGFR2 fusions were significantly less common in fluke-associated CCA (1/121; 0.8%; P = .0006). All FGFR fusions were detected exclusively in intrahepatic CCAs and were mutually exclusive with KRAS/ERBB2/BRAF/FGFR mutations, pointing to their potential roles as oncogenic drivers. CONCLUSION FGFR2 fusions are rare in fluke-associated CCA, underscoring how distinct etiologies may affect molecular landscapes in tumors and highlighting the need to discover other actionable genomic alterations in endemic fluke-associated CCA. |
| first_indexed | 2024-12-13T20:19:52Z |
| format | Article |
| id | doaj.art-10fa1389d83040b8a3bd96d6fb1d277e |
| institution | Directory Open Access Journal |
| issn | 2687-8941 |
| language | English |
| last_indexed | 2024-12-13T20:19:52Z |
| publishDate | 2020-11-01 |
| publisher | American Society of Clinical Oncology |
| record_format | Article |
| series | JCO Global Oncology |
| spelling | doaj.art-10fa1389d83040b8a3bd96d6fb1d277e2022-12-21T23:32:43ZengAmerican Society of Clinical OncologyJCO Global Oncology2687-89412020-11-01662863810.1200/GO.20.00030Lack of Targetable FGFR2 Fusions in Endemic Fluke-Associated CholangiocarcinomaSarinya Kongpetch0Apinya Jusakul1Jing Quan Lim2Cedric Chuan Young Ng3Jason Yongsheng Chan4Vikneswari Rajasegaran5Tse Hui Lim6Kiat Hon Lim7Su Pin Choo8Simona Dima9Irinel Popescu10Dan G. Duda11Veerapol Kukongviriyapan12Narong Khuntikeo13Chawalit Pairojkul14Steven G. Rozen15Patrick Tan16Bin Tean Teh17Cholangiocarcinoma Screening and Care Program and Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, ThailandCholangiocarcinoma Screening and Care Program and Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, ThailandOncology Academic Clinical Program, Duke-NUS Medical School, SingaporeLaboratory of Cancer Epigenome, Division of Medical Science, National Cancer Centre Singapore, SingaporeDivision of Medical Oncology, National Cancer Centre Singapore, SingaporeLaboratory of Cancer Epigenome, Division of Medical Science, National Cancer Centre Singapore, SingaporeCytogenetics Laboratory, Department of Molecular Pathology, Singapore General Hospital, SingaporeDepartment of Anatomical Pathology, Singapore General Hospital, SingaporeDivision of Medical Oncology, National Cancer Centre Singapore, SingaporeCenter of Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute, Bucharest, RomaniaCenter of Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute, Bucharest, RomaniaEdwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MACholangiocarcinoma Screening and Care Program and Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, ThailandCholangiocarcinoma Screening and Care Program and Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, ThailandDepartment of Pathology, Khon Kaen University, Khon Kaen, ThailandProgram in Cancer and Stem Cell Biology, Duke-NUS Medical School, SingaporeProgram in Cancer and Stem Cell Biology, Duke-NUS Medical School, SingaporeLaboratory of Cancer Epigenome, Division of Medical Science, National Cancer Centre Singapore, SingaporePURPOSE Cholangiocarcinoma (CCA) remains a disease with poor prognosis and limited therapeutic options. Identification of driver genetic alterations may lead to the discovery of more effective targeted therapies. CCAs harboring FGFR2 fusions have recently demonstrated promising responses to FGFR inhibitors, highlighting their potential relevance as predictive biomarkers. CCA incidence is high in the northeast of Thailand and its neighboring countries because of chronic infection with the liver fluke Opisthorchis viverrini (Ov). However, there are currently no available data on the prevalence of FGFR alterations in fluke-associated CCA in endemic countries. MATERIALS AND METHODS In this study, we performed anchored multiplex polymerase chain reaction target enrichment RNA sequencing of FGFR1-3, validated by fluorescence in situ hybridization and Sanger sequencing, in 121 Ov-associated and 95 non–Ov-associated CCA tumors. RESULTS Compared with non–fluke-associated CCA (11/95; 11.6%), FGFR2 fusions were significantly less common in fluke-associated CCA (1/121; 0.8%; P = .0006). All FGFR fusions were detected exclusively in intrahepatic CCAs and were mutually exclusive with KRAS/ERBB2/BRAF/FGFR mutations, pointing to their potential roles as oncogenic drivers. CONCLUSION FGFR2 fusions are rare in fluke-associated CCA, underscoring how distinct etiologies may affect molecular landscapes in tumors and highlighting the need to discover other actionable genomic alterations in endemic fluke-associated CCA.https://ascopubs.org/doi/10.1200/GO.20.00030 |
| spellingShingle | Sarinya Kongpetch Apinya Jusakul Jing Quan Lim Cedric Chuan Young Ng Jason Yongsheng Chan Vikneswari Rajasegaran Tse Hui Lim Kiat Hon Lim Su Pin Choo Simona Dima Irinel Popescu Dan G. Duda Veerapol Kukongviriyapan Narong Khuntikeo Chawalit Pairojkul Steven G. Rozen Patrick Tan Bin Tean Teh Lack of Targetable FGFR2 Fusions in Endemic Fluke-Associated Cholangiocarcinoma JCO Global Oncology |
| title | Lack of Targetable FGFR2 Fusions in Endemic Fluke-Associated Cholangiocarcinoma |
| title_full | Lack of Targetable FGFR2 Fusions in Endemic Fluke-Associated Cholangiocarcinoma |
| title_fullStr | Lack of Targetable FGFR2 Fusions in Endemic Fluke-Associated Cholangiocarcinoma |
| title_full_unstemmed | Lack of Targetable FGFR2 Fusions in Endemic Fluke-Associated Cholangiocarcinoma |
| title_short | Lack of Targetable FGFR2 Fusions in Endemic Fluke-Associated Cholangiocarcinoma |
| title_sort | lack of targetable fgfr2 fusions in endemic fluke associated cholangiocarcinoma |
| url | https://ascopubs.org/doi/10.1200/GO.20.00030 |
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