Integrative genomic analyses of European intrahepatic cholangiocarcinoma: Novel ROS1 fusion gene and PBX1 as prognostic marker
Background Cholangiocarcinoma (CCA) is a fatal cancer of the bile duct with a poor prognosis owing to limited therapeutic options. The incidence of intrahepatic CCA (iCCA) is increasing worldwide, and its molecular basis is emerging. Environmental factors may contribute to regional differences in th...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
June 2024
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| In: |
Clinical and translational medicine
Year: 2024, Jahrgang: 14, Heft: 6, Pages: 1-23 |
| ISSN: | 2001-1326 |
| DOI: | 10.1002/ctm2.1723 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1002/ctm2.1723 Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ctm2.1723 
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| Verfasserangaben: | Patrick S. Plum, Timo Hess, Denis Bertrand, Isabelle Morgenstern, Oscar Velazquez Camacho, Christoph Jonas, Christina Alidousty, Britta Wagner, Stephanie Roessler, Thomas Albrecht, Jessica Becker, Vanessa Richartz, Barbara Holz, Sascha Hoppe, Huay Mei Poh, Burton Kuan Hui Chia, Cheryl Xueli Chan, Thushangi Pathiraja, Audrey SM Teo, Jens U. Marquardt, Alexis Khng, Michael Heise, Yao Fei, René Thieme, Sebastian Klein, Jing Han Hong, Simona O Dima, Irinel Popescu, Maria Hoppe-Lotichius, Reinhard Buettner, Anja Lautem, Gerd Otto, Alexander Quaas, Niranjan Nagarajan, Steve Rozen, Bin Tean Teh, Benjamin Goeppert, Uta Drebber, Hauke Lang, Patrick Tan, Ines Gockel, Johannes Schumacher, Axel M. Hillmer |
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| 245 | 1 | 0 | |a Integrative genomic analyses of European intrahepatic cholangiocarcinoma |b Novel ROS1 fusion gene and PBX1 as prognostic marker |c Patrick S. Plum, Timo Hess, Denis Bertrand, Isabelle Morgenstern, Oscar Velazquez Camacho, Christoph Jonas, Christina Alidousty, Britta Wagner, Stephanie Roessler, Thomas Albrecht, Jessica Becker, Vanessa Richartz, Barbara Holz, Sascha Hoppe, Huay Mei Poh, Burton Kuan Hui Chia, Cheryl Xueli Chan, Thushangi Pathiraja, Audrey SM Teo, Jens U. Marquardt, Alexis Khng, Michael Heise, Yao Fei, René Thieme, Sebastian Klein, Jing Han Hong, Simona O Dima, Irinel Popescu, Maria Hoppe-Lotichius, Reinhard Buettner, Anja Lautem, Gerd Otto, Alexander Quaas, Niranjan Nagarajan, Steve Rozen, Bin Tean Teh, Benjamin Goeppert, Uta Drebber, Hauke Lang, Patrick Tan, Ines Gockel, Johannes Schumacher, Axel M. Hillmer |
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| 500 | |a Zuerst veröffentlicht: 14. Juni 2024 | ||
| 500 | |a Gesehen am 29.11.2024 | ||
| 520 | |a Background Cholangiocarcinoma (CCA) is a fatal cancer of the bile duct with a poor prognosis owing to limited therapeutic options. The incidence of intrahepatic CCA (iCCA) is increasing worldwide, and its molecular basis is emerging. Environmental factors may contribute to regional differences in the mutation spectrum of European patients with iCCA, which are underrepresented in systematic genomic and transcriptomic studies of the disease. Methods We describe an integrated whole-exome sequencing and transcriptomic study of 37 iCCAs patients in Germany. Results We observed as most frequently mutated genes ARID1A (14%), IDH1, BAP1, TP53, KRAS, and ATM in 8% of patients. We identified FGFR2::BICC1 fusions in two tumours, and FGFR2::KCTD1 and TMEM106B::ROS1 as novel fusions with potential therapeutic implications in iCCA and confirmed oncogenic properties of TMEM106B::ROS1 in vitro. Using a data integration framework, we identified PBX1 as a novel central regulatory gene in iCCA. We performed extended screening by targeted sequencing of an additional 40 CCAs. In the joint analysis, IDH1 (13%), BAP1 (10%), TP53 (9%), KRAS (7%), ARID1A (7%), NF1 (5%), and ATM (5%) were the most frequently mutated genes, and we found PBX1 to show copy gain in 20% of the tumours. According to other studies, amplifications of PBX1 tend to occur in European iCCAs in contrast to liver fluke-associated Asian iCCAs. Conclusions By analyzing an additional European cohort of iCCA patients, we found that PBX1 protein expression was a marker of poor prognosis. Overall, our findings provide insight into key molecular alterations in iCCA, reveal new targetable fusion genes, and suggest that PBX1 is a novel modulator of this disease. | ||
| 650 | 4 | |a fusion genes | |
| 650 | 4 | |a genomics | |
| 650 | 4 | |a intrahepatic cholangiocarcinoma | |
| 650 | 4 | |a PBX1 | |
| 650 | 4 | |a transcriptomics | |
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| 700 | 1 | |a Holz, Barbara |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hoppe, Sascha |e VerfasserIn |4 aut | |
| 700 | 1 | |a Poh, Huay Mei |e VerfasserIn |4 aut | |
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| 700 | 1 | |a Quaas, Alexander |e VerfasserIn |4 aut | |
| 700 | 1 | |a Nagarajan, Niranjan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rozen, Steve |e VerfasserIn |4 aut | |
| 700 | 1 | |a Teh, Bin Tean |e VerfasserIn |4 aut | |
| 700 | 1 | |a Goeppert, Benjamin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Drebber, Uta |e VerfasserIn |4 aut | |
| 700 | 1 | |a Lang, Hauke |e VerfasserIn |4 aut | |
| 700 | 1 | |a Tan, Patrick |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gockel, Ines |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schumacher, Johannes |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hillmer, Axel M. |e VerfasserIn |4 aut | |
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