| A genome-wide association analysis of temozolomide response using lymphoblastoid cell lines shows a clinically relevant association with MGMT. | |
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MedLine Citation:
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PMID: 23047291 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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OBJECTIVE: Recently, lymphoblastoid cell lines (LCLs) have emerged as an innovative model system for mapping gene variants that predict the dose response to chemotherapy drugs. METHODS: In the current study, this strategy was expanded to the in-vitro genome-wide association approach, using 516 LCLs derived from a White cohort to assess the cytotoxic response to temozolomide. RESULTS: Genome-wide association analysis using ∼2.1 million quality-controlled single-nucleotide polymorphisms (SNPs) identified a statistically significant association (P<10) with SNPs in the O-methylguanine-DNA methyltransferase (MGMT) gene. We also show that the primary SNP in this region is significantly associated with the differential gene expression of MGMT (P<10) in LCLs and differential methylation in glioblastoma samples from The Cancer Genome Atlas. CONCLUSION: The previously documented clinical and functional relationships between MGMT and temozolomide response highlight the potential of well-powered genome-wide association studies of the LCL model system to identify meaningful genetic associations. |
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Authors:
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Chad C Brown; Tammy M Havener; Marisa W Medina; J Todd Auman; Lara M Mangravite; Ronald M Krauss; Howard L McLeod; Alison A Motsinger-Reif |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Pharmacogenetics and genomics Volume: 22 ISSN: 1744-6880 ISO Abbreviation: Pharmacogenet. Genomics Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-10-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101231005 Medline TA: Pharmacogenet Genomics Country: United States |
Other Details:
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Languages: eng Pagination: 796-802 Citation Subset: IM |
Affiliation:
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aDepartment of Statistics bBioinformatics Research Center, North Carolina State University, Raleigh cInstitute for Pharmacogenomics and Individualized Therapy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina dChildren's Hospital Oakland Research Institute, Oakland, California eSage Bionetworks, Seattle, Washington, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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