Scheiter, Alexander and Hierl, Frederik and Winkel, Ingrid and Keil, Felix and Klier-Richter, Margit and Coulouarn, Cedric and Lueke, Florian and Kandulski, Arne and Evert, Matthias and Dietmaier, Wolfgang and Calvisi, Diego F. and Utpatel, Kirsten (2022) Wnt/beta-Catenin-Pathway Alterations and Homologous Recombination Deficiency in Cholangiocarcinoma Cell Lines and Clinical Samples: Towards Specific Vulnerabilities. JOURNAL OF PERSONALIZED MEDICINE, 12 (8): 1270. ISSN , 2075-4426
Full text not available from this repository. (Request a copy)Abstract
Cholangiocarcinoma (CCA) features a dismal prognosis with limited treatment options. Genomic studies have unveiled several promising targets in this disease, including fibroblast growth factor receptor (FGFR) fusions and isocitrate dehydrogenase (IDH) mutations. To fully harness the potential of genomically informed therapies in CCA, it is necessary to thoroughly characterize the available model organisms, including cell lines. One parameter to investigate in CCA is homologous recombination deficiency (HRD). While mutations in homologous recombinational repair (HRR)-related genes have been detected, their predictive value remains undetermined. Using a targeted next-generation sequencing approach, we analyzed 12 human CCA cell lines and compared them to 62 CCA samples of the molecular tumor board cohort. The AmoyDx (R) HRD Focus Panel was employed to determine corresponding genomic scar scores (GSS). Ten of twelve cell lines harbored alterations in common HRR-related genes, and five cell lines were HRD-positive, although this parameter did not correlate well with Olaparib sensitivity. Moreover, functionally relevant APC and beta-catenin mutations were registered, which were also detected in 4/176 (2.3%) samples on a CCA microarray. Although rare, these alterations were exclusive to large duct type CCA with associated intraductal papillary neoplasms of the bile duct (IPNB) in 3 cases, pointing at a distinct form of cholangiocarcinogenesis with potential specific vulnerabilities.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INTRAHEPATIC CHOLANGIOCARCINOMA; BETA-CATENIN; PHASE-I; CANCER; MUTATIONS; OLAPARIB; TRANSCRIPTION; CHEMOTHERAPY; MECHANISMS; INHIBITOR; cholangiocarcinoma; beta-catenin; WNT; APC; HRD; Olaparib; PARP; intraductal papillary neoplasm of the bile duct |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Dec 2023 10:43 |
| Last Modified: | 12 Dec 2023 10:43 |
| URI: | https://pred.uni-regensburg.de/id/eprint/57009 |
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