Gutenberg Open Science: Identification of novel rare ABCC1 transporter mutations in tumor biopsies of cancer patients

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-5642

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DC Field	Value	Language
dc.contributor.author	Kadioglu, Onat	-
dc.contributor.author	Saeed, Mohamed	-
dc.contributor.author	Munder, Markus	-
dc.contributor.author	Spuller, Andreas	-
dc.contributor.author	Greten, Henry Johannes	-
dc.contributor.author	Efferth, Thomas	-
dc.date.accessioned	2021-02-09T10:07:27Z	-
dc.date.available	2021-02-09T10:07:27Z	-
dc.date.issued	2020	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/5646	-
dc.description.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.	en_GB
dc.description.sponsorship	DFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin Mainz	de
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	570 Biowissenschaften	de_DE
dc.subject.ddc	570 Life sciences	en_GB
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	Identification of novel rare ABCC1 transporter mutations in tumor biopsies of cancer patients	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-5642	-
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 04 Medizin	de
jgu.organisation.department	FB 09 Chemie, Pharmazie u. Geowissensch.	de
jgu.organisation.number	2700	-
jgu.organisation.number	7950	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	Cells	de
jgu.journal.volume	9	de
jgu.journal.issue	2	de
jgu.pages.alternative	299	de
jgu.publisher.year	2020	-
jgu.publisher.name	MDPI	de
jgu.publisher.place	Basel	de
jgu.publisher.uri	https://doi.org/10.3390/cells9020299	de
jgu.publisher.issn	2073-4409	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	570	de
jgu.subject.ddccode	610	de
jgu.publisher.doi	10.3390/cells9020299
jgu.organisation.ror	https://ror.org/023b0x485
Appears in collections:	JGU-Publikationen

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