High-throughput screening and genome-wide analyses of 44 anticancer drugs in the 1000 Genomes cell lines reveals an association of the NQO1 gene with the response of multiple anticancer drugs.

Cancer patients exhibit a broad range of inter-individual variability in response and toxicity to widely used anticancer drugs, and genetic variation is a major contributor to this variability. To identify new genes that influence the response of 44 FDA-approved anticancer drug treatments widely use...

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Autores principales:	Farida S Akhtari, Adrian J Green, George W Small, Tammy M Havener, John S House, Kyle R Roell, David M Reif, Howard L McLeod, Timothy Wiltshire, Alison A Motsinger-Reif
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/f1416aa594d345ff9d7fa52334c49271
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spelling	oai:doaj.org-article:f1416aa594d345ff9d7fa52334c492712021-12-02T20:02:51ZHigh-throughput screening and genome-wide analyses of 44 anticancer drugs in the 1000 Genomes cell lines reveals an association of the NQO1 gene with the response of multiple anticancer drugs.1553-73901553-740410.1371/journal.pgen.1009732https://doaj.org/article/f1416aa594d345ff9d7fa52334c492712021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009732https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Cancer patients exhibit a broad range of inter-individual variability in response and toxicity to widely used anticancer drugs, and genetic variation is a major contributor to this variability. To identify new genes that influence the response of 44 FDA-approved anticancer drug treatments widely used to treat various types of cancer, we conducted high-throughput screening and genome-wide association mapping using 680 lymphoblastoid cell lines from the 1000 Genomes Project. The drug treatments considered in this study represent nine drug classes widely used in the treatment of cancer in addition to the paclitaxel + epirubicin combination therapy commonly used for breast cancer patients. Our genome-wide association study (GWAS) found several significant and suggestive associations. We prioritized consistent associations for functional follow-up using gene-expression analyses. The NAD(P)H quinone dehydrogenase 1 (NQO1) gene was found to be associated with the dose-response of arsenic trioxide, erlotinib, trametinib, and a combination treatment of paclitaxel + epirubicin. NQO1 has previously been shown as a biomarker of epirubicin response, but our results reveal novel associations with these additional treatments. Baseline gene expression of NQO1 was positively correlated with response for 43 of the 44 treatments surveyed. By interrogating the functional mechanisms of this association, the results demonstrate differences in both baseline and drug-exposed induction.Farida S AkhtariAdrian J GreenGeorge W SmallTammy M HavenerJohn S HouseKyle R RoellDavid M ReifHoward L McLeodTimothy WiltshireAlison A Motsinger-ReifPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 8, p e1009732 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Farida S Akhtari Adrian J Green George W Small Tammy M Havener John S House Kyle R Roell David M Reif Howard L McLeod Timothy Wiltshire Alison A Motsinger-Reif High-throughput screening and genome-wide analyses of 44 anticancer drugs in the 1000 Genomes cell lines reveals an association of the NQO1 gene with the response of multiple anticancer drugs.
description	Cancer patients exhibit a broad range of inter-individual variability in response and toxicity to widely used anticancer drugs, and genetic variation is a major contributor to this variability. To identify new genes that influence the response of 44 FDA-approved anticancer drug treatments widely used to treat various types of cancer, we conducted high-throughput screening and genome-wide association mapping using 680 lymphoblastoid cell lines from the 1000 Genomes Project. The drug treatments considered in this study represent nine drug classes widely used in the treatment of cancer in addition to the paclitaxel + epirubicin combination therapy commonly used for breast cancer patients. Our genome-wide association study (GWAS) found several significant and suggestive associations. We prioritized consistent associations for functional follow-up using gene-expression analyses. The NAD(P)H quinone dehydrogenase 1 (NQO1) gene was found to be associated with the dose-response of arsenic trioxide, erlotinib, trametinib, and a combination treatment of paclitaxel + epirubicin. NQO1 has previously been shown as a biomarker of epirubicin response, but our results reveal novel associations with these additional treatments. Baseline gene expression of NQO1 was positively correlated with response for 43 of the 44 treatments surveyed. By interrogating the functional mechanisms of this association, the results demonstrate differences in both baseline and drug-exposed induction.
format	article
author	Farida S Akhtari Adrian J Green George W Small Tammy M Havener John S House Kyle R Roell David M Reif Howard L McLeod Timothy Wiltshire Alison A Motsinger-Reif
author_facet	Farida S Akhtari Adrian J Green George W Small Tammy M Havener John S House Kyle R Roell David M Reif Howard L McLeod Timothy Wiltshire Alison A Motsinger-Reif
author_sort	Farida S Akhtari
title	High-throughput screening and genome-wide analyses of 44 anticancer drugs in the 1000 Genomes cell lines reveals an association of the NQO1 gene with the response of multiple anticancer drugs.
title_short	High-throughput screening and genome-wide analyses of 44 anticancer drugs in the 1000 Genomes cell lines reveals an association of the NQO1 gene with the response of multiple anticancer drugs.
title_full	High-throughput screening and genome-wide analyses of 44 anticancer drugs in the 1000 Genomes cell lines reveals an association of the NQO1 gene with the response of multiple anticancer drugs.
title_fullStr	High-throughput screening and genome-wide analyses of 44 anticancer drugs in the 1000 Genomes cell lines reveals an association of the NQO1 gene with the response of multiple anticancer drugs.
title_full_unstemmed	High-throughput screening and genome-wide analyses of 44 anticancer drugs in the 1000 Genomes cell lines reveals an association of the NQO1 gene with the response of multiple anticancer drugs.
title_sort	high-throughput screening and genome-wide analyses of 44 anticancer drugs in the 1000 genomes cell lines reveals an association of the nqo1 gene with the response of multiple anticancer drugs.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/f1416aa594d345ff9d7fa52334c49271
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High-throughput screening and genome-wide analyses of 44 anticancer drugs in the 1000 Genomes cell lines reveals an association of the NQO1 gene with the response of multiple anticancer drugs.

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