Integrative genomic analyses of European intrahepatic cholangiocarcinoma: Novel ROS1 fusion gene and PBX1 as prognostic marker Article Swipe
Patrick Sven Plum
,
Timo Hess
,
Denis Bertrand
,
Isabelle Morgenstern
,
Oscar Velázquez Camacho
,
Christoph Jonas
,
Christina Alidousty
,
B. Wagner
,
Stéphanie Roessler
,
Thomas Albrecht
,
J Becker
,
Vanessa Richartz
,
Barbara Holz
,
Sascha Hoppe
,
Huay Mei Poh
,
Burton Kuan Hui Chia
,
Cheryl Xueli Chan
,
Thushangi N. Pathiraja
,
Audrey S.M. Teo
,
Jens U. Marquardt
,
Alexis Jiaying Khng
,
Michael Heise
,
Fei Yao
,
René Thieme
,
Sebastian Klein
,
Jing Han Hong
,
Simona 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
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1002/ctm2.1723
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1002/ctm2.1723
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.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/ctm2.1723
- https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ctm2.1723
- OA Status
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- Cited By
- 4
- References
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- Related Works
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- OpenAlex ID
- https://openalex.org/W4399708128
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Raw OpenAlex JSON
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https://openalex.org/W4399708128Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1002/ctm2.1723Digital Object Identifier
- Title
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Integrative genomic analyses of European intrahepatic cholangiocarcinoma: Novel ROS1 fusion gene and PBX1 as prognostic markerWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-06-01Full publication date if available
- Authors
-
Patrick Sven Plum, Timo Hess, Denis Bertrand, Isabelle Morgenstern, Oscar Velázquez Camacho, Christoph Jonas, Christina Alidousty, B. Wagner, Stéphanie Roessler, Thomas Albrecht, J Becker, Vanessa Richartz, Barbara Holz, Sascha Hoppe, Huay Mei Poh, Burton Kuan Hui Chia, Cheryl Xueli Chan, Thushangi N. Pathiraja, Audrey S.M. Teo, Jens U. Marquardt, Alexis Jiaying Khng, Michael Heise, Fei Yao, René Thieme, Sebastian Klein, Jing Han Hong, Simona 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. HillmerList of authors in order
- Landing page
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https://doi.org/10.1002/ctm2.1723Publisher landing page
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ctm2.1723Direct link to full text PDF
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
- OA URL
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ctm2.1723Direct OA link when available
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Intrahepatic Cholangiocarcinoma, Medicine, Fusion gene, Internal medicine, Incidence (geometry), Bile duct cancer, Oncology, Disease, Cancer, Bioinformatics, Gene, Biology, Genetics, Optics, PhysicsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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4Total citation count in OpenAlex
- Citations by year (recent)
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2025: 3, 2024: 1Per-year citation counts (last 5 years)
- References (count)
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110Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.(14%), | 89 |
| abstract_inverted_index.(iCCA) | 26 |
| abstract_inverted_index.ARID1A | 88, 170 |
| abstract_inverted_index.cancer | 7 |
| abstract_inverted_index.cohort | 222 |
| abstract_inverted_index.fusion | 252 |
| abstract_inverted_index.genes, | 182, 253 |
| abstract_inverted_index.iCCAs. | 215 |
| abstract_inverted_index.marker | 234 |
| abstract_inverted_index.reveal | 249 |
| abstract_inverted_index.Methods | 64 |
| abstract_inverted_index.Results | 80 |
| abstract_inverted_index.central | 141 |
| abstract_inverted_index.factors | 37 |
| abstract_inverted_index.fusions | 104, 114 |
| abstract_inverted_index.genomic | 57 |
| abstract_inverted_index.insight | 242 |
| abstract_inverted_index.limited | 18 |
| abstract_inverted_index.mutated | 86, 181 |
| abstract_inverted_index.protein | 230 |
| abstract_inverted_index.provide | 241 |
| abstract_inverted_index.studies | 60 |
| abstract_inverted_index.suggest | 255 |
| abstract_inverted_index.Abstract | 0 |
| abstract_inverted_index.European | 48, 207, 221 |
| abstract_inverted_index.Germany. | 79 |
| abstract_inverted_index.Overall, | 238 |
| abstract_inverted_index.contrast | 210 |
| abstract_inverted_index.describe | 66 |
| abstract_inverted_index.disease. | 63, 264 |
| abstract_inverted_index.extended | 148 |
| abstract_inverted_index.findings | 240 |
| abstract_inverted_index.mutation | 45 |
| abstract_inverted_index.observed | 82 |
| abstract_inverted_index.options. | 20 |
| abstract_inverted_index.patients | 49, 77 |
| abstract_inverted_index.regional | 41 |
| abstract_inverted_index.spectrum | 46 |
| abstract_inverted_index.studies, | 199 |
| abstract_inverted_index.targeted | 151 |
| abstract_inverted_index.tumours, | 107 |
| abstract_inverted_index.tumours. | 195 |
| abstract_inverted_index.According | 196 |
| abstract_inverted_index.analysis, | 161 |
| abstract_inverted_index.analyzing | 218 |
| abstract_inverted_index.confirmed | 122 |
| abstract_inverted_index.emerging. | 35 |
| abstract_inverted_index.incidence | 22 |
| abstract_inverted_index.modulator | 261 |
| abstract_inverted_index.molecular | 32, 245 |
| abstract_inverted_index.oncogenic | 123 |
| abstract_inverted_index.patients, | 225 |
| abstract_inverted_index.patients. | 100 |
| abstract_inverted_index.performed | 147 |
| abstract_inverted_index.potential | 116 |
| abstract_inverted_index.prognosis | 15 |
| abstract_inverted_index.screening | 149 |
| abstract_inverted_index.Background | 1 |
| abstract_inverted_index.additional | 155, 220 |
| abstract_inverted_index.contribute | 39 |
| abstract_inverted_index.expression | 231 |
| abstract_inverted_index.framework, | 134 |
| abstract_inverted_index.frequently | 85, 180 |
| abstract_inverted_index.identified | 102, 136 |
| abstract_inverted_index.increasing | 28 |
| abstract_inverted_index.integrated | 68 |
| abstract_inverted_index.prognosis. | 237 |
| abstract_inverted_index.properties | 124 |
| abstract_inverted_index.regulatory | 142 |
| abstract_inverted_index.sequencing | 70, 152 |
| abstract_inverted_index.systematic | 56 |
| abstract_inverted_index.targetable | 251 |
| abstract_inverted_index.worldwide, | 29 |
| abstract_inverted_index.Conclusions | 216 |
| abstract_inverted_index.alterations | 246 |
| abstract_inverted_index.differences | 42 |
| abstract_inverted_index.integration | 133 |
| abstract_inverted_index.therapeutic | 19, 117 |
| abstract_inverted_index.FGFR2::BICC1 | 103 |
| abstract_inverted_index.FGFR2::KCTD1 | 109 |
| abstract_inverted_index.implications | 118 |
| abstract_inverted_index.intrahepatic | 24 |
| abstract_inverted_index.Environmental | 36 |
| abstract_inverted_index.whole‐exome | 69 |
| abstract_inverted_index.TMEM106B::ROS1 | 111, 126 |
| abstract_inverted_index.amplifications | 200 |
| abstract_inverted_index.transcriptomic | 59, 72 |
| abstract_inverted_index.underrepresented | 54 |
| abstract_inverted_index.Cholangiocarcinoma | 2 |
| abstract_inverted_index.fluke‐associated | 213 |
| cited_by_percentile_year.max | 98 |
| cited_by_percentile_year.min | 90 |
| corresponding_author_ids | https://openalex.org/A5081765599, https://openalex.org/A5042877889 |
| countries_distinct_count | 5 |
| institutions_distinct_count | 43 |
| corresponding_institution_ids | https://openalex.org/I115228651, https://openalex.org/I161103922, https://openalex.org/I180923762, https://openalex.org/I4210153755, https://openalex.org/I66068411 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/1 |
| sustainable_development_goals[0].score | 0.6200000047683716 |
| sustainable_development_goals[0].display_name | No poverty |
| citation_normalized_percentile.value | 0.91435919 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |