Identification of genetic variants contributing to cisplatin-induced cytotoxicity by use of a genomewide approach.

Identification of genetic variants contributing to cisplatin-induced cytotoxicity by use of a genomewide approach. Research Abstract Details 

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Identification of genetic variants contributing to cisplatin-induced cytotoxicity by use of a genomewide approach. Abstract Text:

R Stephanie Huang,Shiwei Duan,Sunita J Shukla,Emily O Kistner,Tyson A Clark,Tina X Chen,Anthony C Schweitzer,John E Blume,M Eileen Dolan,

Cisplatin, a platinating agent commonly used to treat several cancers, is associated with nephrotoxicity, neurotoxicity, and ototoxicity, which has hindered its utility. To gain a better understanding of the genetic variants associated with cisplatin-induced toxicity, we present a stepwise approach integrating genotypes, gene expression, and sensitivity of HapMap cell lines to cisplatin. Cell lines derived from 30 trios of European descent (CEU) and 30 trios of African descent (YRI) were used to develop a preclinical model to identify genetic variants and gene expression that contribute to cisplatin-induced cytotoxicity in two different populations. Cytotoxicity was determined as cell-growth inhibition at increasing concentrations of cisplatin for 48 h. Gene expression in 176 HapMap cell lines (87 CEU and 89 YRI) was determined using the Affymetrix GeneChip Human Exon 1.0 ST Array. We identified six, two, and nine representative SNPs that contribute to cisplatin-induced cytotoxicity through their effects on 8, 2, and 16 gene expressions in the combined, Centre d'Etude du Polymorphisme Humain (CEPH), and Yoruban populations, respectively. These genetic variants contribute to 27%, 29%, and 45% of the overall variation in cell sensitivity to cisplatin in the combined, CEPH, and Yoruban populations, respectively. Our whole-genome approach can be used to elucidate the expression of quantitative trait loci contributing to a wide range of cellular phenotypes.

Identification of genetic variants contributing to cisplatin-induced cytotoxicity by use of a genomewide approach. Publishing Authors By Initials

RS Huang,S Duan,SJ Shukla,EO Kistner,TA Clark,TX Chen,AC Schweitzer,JE Blume,ME Dolan,

For similar genetic structures: genome: genome components: genes: quantitative trait loci research abstracts see: genetic structures: genome: genome components: genes: quantitative trait loci research

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Identification of genetic variants contributing to cisplatin-induced cytotoxicity by use of a genomewide approach. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: American journal of human genetics

VOLUME: 81

Page Numbers: 427-37

Journal Abbreviation: Am. J. Hum. Genet.

ISSN: 0002-9297

DAY: 1

MONTH: 08

YEAR: 2007

Identification of genetic variants contributing to cisplatin-induced cytotoxicity by use of a genomewide approach. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370475

Identification of genetic variants contributing to cisplatin-induced cytotoxicity by use of a genomewide approach. Keywords Mesh Terms:

KEYWORDS: Quantitative Trait Loci

MESH TERMS: genetics

Chemical & Substance for Abstract: Identification of genetic variants contributing to cisplatin-induced cytotoxicity by use of a genomewide approach. Information

Substance Name: Cisplatin

Registry Number: 15663-27-1

Grant and Affiliation Information for Identification of genetic variants contributing to cisplatin-induced cytotoxicity by use of a genomewide approach.

AFFILIATION: Department of Medicine, University of Chicago, Chicago, IL 60637, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM61393

ACRONYM: GM

MEDLINETA: Am J Hum Genet

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