Identification of Novel Rare ABCC1 Transporter Mutations in Tumor Biopsies of Cancer Patients
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Onat Kadioglu
- Mohamed Saeed
- Markus Munder
- Andreas Spuller
- Henry Johannes Greten
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000521944900040&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.3390/cells9020299
- eISSN
- 2073-4409
- Externe Identifier
- Clarivate Analytics Document Solution ID: KX5UC
- PubMed Identifier: 31991926
- Ausgabe der Veröffentlichung
- 2
- Zeitschrift
- CELLS
- Schlüsselwörter
- ABC transporters
- cancer
- multidrug resistance
- Artikelnummer
- ARTN 299
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Titel
- Identification of Novel Rare <i>ABCC1</i> Transporter Mutations in Tumor Biopsies of Cancer Patients
- Sub types
- Article
- Ausgabe der Zeitschrift
- 9
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Abstract
- <jats:p>The efficiency of chemotherapy drugs can be affected by ATP-binding cassette (ABC) transporter expression or by their mutation status. Multidrug resistance is linked with ABC transporter overexpression. In the present study, we performed rare mutation analyses for 12 ABC transporters related to drug resistance (ABCA2, -A3, -B1, -B2, -B5, -C1, -C2, -C3, -C4, -C5, -C6, -G2) in a dataset of 18 cancer patients. We focused on rare mutations resembling tumor heterogeneity of ABC transporters in small tumor subpopulations. Novel rare mutations were found in ABCC1, but not in the other ABC transporters investigated. Diverse ABCC1 mutations were found, including nonsense mutations causing premature stop codons, and compared with the wild-type protein in terms of their protein structure. Nonsense mutations lead to truncated protein structures. Molecular docking and heat map analyses of ABCC1/MRP1 pointed out that Lys498* appeared in a separate cluster branch due to the large deletion, leading to a massive disruption in the protein conformation. The resulting proteins, which are nonfunctional due to nonsense mutations in tumors, offer a promising chemotherapy strategy since tumors with nonsense mutations may be more sensitive to anticancer drugs than wild-type ABCC1-expressing tumors. This could provide a novel tumor-specific toxicity strategy and a way to overcome drug resistance.</jats:p>
- Autoren
- Onat Kadioglu
- Mohamed Saeed
- Markus Munder
- Andreas Spuller
- Henry Johannes Greten
- Thomas Efferth
- DOI
- 10.3390/cells9020299
- eISSN
- 2073-4409
- Ausgabe der Veröffentlichung
- 2
- Zeitschrift
- Cells
- Sprache
- en
- Online publication date
- 2020
- Paginierung
- 299 - 299
- Status
- Published online
- Herausgeber
- MDPI AG
- Herausgeber URL
- http://dx.doi.org/10.3390/cells9020299
- Datum der Datenerfassung
- 2020
- Titel
- Identification of Novel Rare ABCC1 Transporter Mutations in Tumor Biopsies of Cancer Patients
- Ausgabe der Zeitschrift
- 9
Data source: Crossref
- Abstract
- <b>:</b> The efficiency of chemotherapy drugs can be affected by ATP-binding cassette (ABC) transporter expression or by their mutation status. Multidrug resistance is linked with ABC transporter overexpression. In the present study, we performed rare mutation analyses for 12 <i>ABC</i> transporters related to drug resistance (ABCA2, -A3, -B1, -B2, -B5, -C1, -C2, -C3, -C4, -C5, -C6, -G2) in a dataset of 18 cancer patients. We focused on rare mutations resembling tumor heterogeneity of ABC transporters in small tumor subpopulations. Novel rare mutations were found in <i>ABCC1</i>, but not in the other ABC transporters investigated. Diverse <i>ABCC1</i> mutations were found, including nonsense mutations causing premature stop codons, and compared with the wild-type protein in terms of their protein structure. Nonsense mutations lead to truncated protein structures. Molecular docking and heat map analyses of <i>ABCC1</i>/MRP1 pointed out that Lys498* appeared in a separate cluster branch due to the large deletion, leading to a massive disruption in the protein conformation. The resulting proteins, which are nonfunctional due to nonsense mutations in tumors, offer a promising chemotherapy strategy since tumors with nonsense mutations may be more sensitive to anticancer drugs than wild-type <i>ABCC1</i>-expressing tumors. This could provide a novel tumor-specific toxicity strategy and a way to overcome drug resistance.
- Addresses
- Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, 55128 Mainz, Germany.
- Autoren
- Onat Kadioglu
- Mohamed Saeed
- Markus Munder
- Andreas Spuller
- Henry Johannes Greten
- Thomas Efferth
- DOI
- 10.3390/cells9020299
- eISSN
- 2073-4409
- Externe Identifier
- PubMed Identifier: 31991926
- PubMed Central ID: PMC7072590
- Open access
- true
- ISSN
- 2073-4409
- Ausgabe der Veröffentlichung
- 2
- Zeitschrift
- Cells
- Schlüsselwörter
- Humans
- Neoplasms
- ATP-Binding Cassette Transporters
- Multidrug Resistance-Associated Proteins
- Codon, Nonsense
- Drug Resistance, Multiple
- Polymorphism, Single Nucleotide
- Female
- Male
- Molecular Docking Simulation
- Sprache
- eng
- Medium
- Electronic
- Online publication date
- 2020
- Open access status
- Open Access
- Paginierung
- E299
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2020
- Titel
- Identification of Novel Rare <i>ABCC1</i> Transporter Mutations in Tumor Biopsies of Cancer Patients.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 9
Files
https://www.mdpi.com/2073-4409/9/2/299/pdf?version=1583049547 https://europepmc.org/articles/PMC7072590?pdf=render
Data source: Europe PubMed Central
- Abstract
- : The efficiency of chemotherapy drugs can be affected by ATP-binding cassette (ABC) transporter expression or by their mutation status. Multidrug resistance is linked with ABC transporter overexpression. In the present study, we performed rare mutation analyses for 12 ABC transporters related to drug resistance (ABCA2, -A3, -B1, -B2, -B5, -C1, -C2, -C3, -C4, -C5, -C6, -G2) in a dataset of 18 cancer patients. We focused on rare mutations resembling tumor heterogeneity of ABC transporters in small tumor subpopulations. Novel rare mutations were found in ABCC1, but not in the other ABC transporters investigated. Diverse ABCC1 mutations were found, including nonsense mutations causing premature stop codons, and compared with the wild-type protein in terms of their protein structure. Nonsense mutations lead to truncated protein structures. Molecular docking and heat map analyses of ABCC1/MRP1 pointed out that Lys498* appeared in a separate cluster branch due to the large deletion, leading to a massive disruption in the protein conformation. The resulting proteins, which are nonfunctional due to nonsense mutations in tumors, offer a promising chemotherapy strategy since tumors with nonsense mutations may be more sensitive to anticancer drugs than wild-type ABCC1-expressing tumors. This could provide a novel tumor-specific toxicity strategy and a way to overcome drug resistance.
- Date of acceptance
- 2020
- Autoren
- Onat Kadioglu
- Mohamed Saeed
- Markus Munder
- Andreas Spuller
- Henry Johannes Greten
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/31991926
- DOI
- 10.3390/cells9020299
- eISSN
- 2073-4409
- Externe Identifier
- PubMed Central ID: PMC7072590
- Ausgabe der Veröffentlichung
- 2
- Zeitschrift
- Cells
- Schlüsselwörter
- ABC transporters
- cancer
- multidrug resistance
- ATP-Binding Cassette Transporters
- Codon, Nonsense
- Drug Resistance, Multiple
- Female
- Humans
- Male
- Molecular Docking Simulation
- Multidrug Resistance-Associated Proteins
- Neoplasms
- Polymorphism, Single Nucleotide
- Sprache
- eng
- Country
- Switzerland
- PII
- cells9020299
- Datum der Veröffentlichung
- 2020
- Status
- Published online
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2020
- Titel
- Identification of Novel Rare ABCC1 Transporter Mutations in Tumor Biopsies of Cancer Patients.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 9
Data source: PubMed
- Author's licence
- CC-BY
- Autoren
- Onat Kadioglu
- Mohamed Saeed
- Markus Munder
- Andreas Spuller
- Henry Johannes Greten
- Thomas Efferth
- Hosting institution
- Universitätsbibliothek Mainz
- Sammlungen
- JGU-Publikationen
- Resource version
- Published version
- DOI
- 10.3390/cells9020299
- Funding acknowledgements
- DFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin Mainz
- File(s) embargoed
- false
- Open access
- true
- ISSN
- 2073-4409
- Ausgabe der Veröffentlichung
- 2
- Zeitschrift
- Cells
- Schlüsselwörter
- 570 Biowissenschaften
- 570 Life sciences
- 610 Medizin
- 610 Medical sciences
- Sprache
- eng
- Open access status
- Open Access
- Paginierung
- 299
- Datum der Veröffentlichung
- 2020
- Public URL
- https://openscience.ub.uni-mainz.de/handle/20.500.12030/5646
- Herausgeber
- MDPI
- Herausgeber URL
- https://doi.org/10.3390/cells9020299
- Datum der Datenerfassung
- 2021
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2021
- Zugang
- Public
- Titel
- Identification of novel rare ABCC1 transporter mutations in tumor biopsies of cancer patients
- Ausgabe der Zeitschrift
- 9
Files
kadioglu_onat-identification-20210209101413928.pdf
Data source: OPENSCIENCE.UB
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