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Titel: Genome-Wide Meta-Analysis Identifies Variants in DSCAM and PDLIM3 That Correlate with Efficacy Outcomes in Metastatic Renal Cell Carcinoma Patients Treated with Sunitinib
VerfasserIn: Diekstra, Meta H. M.
Swen, Jesse J.
van der Zanden, Loes F. M.
Vermeulen, Sita H.
Boven, Epie
Mathijssen, Ron H. J.
Fukunaga, Koya
Mushiroda, Taisei
Hongo, Fumiya
Oosterwijk, Egbert
Cambon-Thomsen, Anne
Castellano, Daniel
Fritsch, Achim
Donas, Jesus Garcia
Rodriguez-Antona, Cristina
Ruijtenbeek, Rob
Radu, Marius T.
Eisen, Tim
Junker, Kerstin UdsID
Roessler, Max
Jaehde, Ulrich
Miki, Tsuneharu
Böhringer, Stefan
Kubo, Michiaki
Kiemeney, Lambertus A. L. M.
Guchelaar, Henk-Jan
Sprache: Englisch
In:
Titel: Cancers
Bandnummer: 14
Heft: 12
Verlag/Plattform: MDPI
Erscheinungsjahr: 2022
Freie Schlagwörter: genome wide association study
sunitinib
pharmacogenetics
metastatic renal cell carcinoma
clear cell renal cell carcinoma
single nucleotide polymorphism
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Individual response to sunitinib in metastatic renal cell carcinoma (mRCC) patients is highly variable. Earlier, sunitinib outcome was related to single nucleotide polymorphisms (SNPs) in CYP3A5 and ABCB1. Our aim is to provide novel insights into biological mechanisms underlying sunitinib action. We included mRCC patients from the European EuroTARGET consortium (n = 550) and the RIKEN cohort in Japan (n = 204) which were analysed separately and in a meta-analysis of genome-wide association studies (GWAS). SNPs were tested for association with progression-free survival (PFS) and overall survival (OS) using Cox regression. Summary statistics were combined using a fixed effect meta-analysis. SNP rs28520013 in PDLIM3 and the correlated SNPs rs2205096 and rs111356738 both in DSCAM, showed genome-wide significance (p < 5 × 10−8 ) with PFS and OS in the meta-analysis. The variant T-allele of rs28520013 associated with an inferior PFS of 5.1 months compared to 12.5 months in non-carriers (p = 4.02 × 10−10, HR = 7.26). T-allele carriers of rs28520013 showed an inferior OS of 6.9 months versus 30.2 months in non-carriers (p = 1.62 × 10−8 , HR = 5.96). In this GWAS we identified novel genetic variants in PDLIM3 and DSCAM that impact PFS and OS in mRCC patients receiving sunitinib. The underlying link between the identified genes and the molecular mechanisms of sunitinib action needs to be elucidated.
DOI der Erstveröffentlichung: 10.3390/cancers14122838
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-365716
hdl:20.500.11880/33222
http://dx.doi.org/10.22028/D291-36571
ISSN: 2072-6694
Datum des Eintrags: 24-Jun-2022
Bezeichnung des in Beziehung stehenden Objekts: Supplementary Materials
In Beziehung stehendes Objekt: https://www.mdpi.com/article/10.3390/cancers14122838/s1
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Urologie und Kinderurologie
Professur: M - Prof. Dr. Michael Stöckle
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes



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