Autor: |
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 |
Jazyk: |
angličtina |
Rok vydání: |
2020 |
Předmět: |
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Zdroj: |
JCO Global Oncology, Vol , Iss 6, Pp 628-638 (2020) |
Druh dokumentu: |
article |
ISSN: |
2687-8941 |
DOI: |
10.1200/GO.20.00030 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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