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Review
. 2012 Jan;13(1):55-70.
doi: 10.2217/pgs.11.121.

Lymphoblastoid cell lines in pharmacogenomic discovery and clinical translation

Heather E Wheeler  1 , M Eileen Dolan
Affiliations
Review

Lymphoblastoid cell lines in pharmacogenomic discovery and clinical translation

Heather E Wheeler et al. Pharmacogenomics. 2012 Jan.

Abstract

The ability to predict how an individual patient will respond to a particular treatment is the ambitious goal of personalized medicine. The genetic make up of an individual has been shown to play a role in drug response. For pharmacogenomic studies, human lymphoblastoid cell lines (LCLs) comprise a useful model system for identifying genetic variants associated with pharmacologic phenotypes. The availability of extensive genotype data for many panels of LCLs derived from individuals of diverse ancestry allows for the study of genetic variants contributing to interethnic and interindividual variation in susceptibility to drugs. Many genome-wide association studies for drug-induced phenotypes have been performed in LCLs, often incorporating gene-expression data. LCLs are also being used in follow-up studies to clinical findings to determine how an associated variant functions to affect phenotype. This review describes the most recent pharmacogenomic findings made in LCLs, including the translation of some findings to clinical cohorts.

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Figures

Figure 1
Figure 1. Potential research design flows for pharmacogenomics studies that utilize the lymphoblastoid cell lines model
GWA: Genome-wide association; LCL: Lymphoblastoid cell line.
See this image and copyright information in PMC

References

    1. Welsh M, Mangravite L, Medina MW, et al. Pharmacogenomic discovery using cell-based models. Pharmacol Rev. 2009;61(4):413–429. Comprehensive review of pharmacogenomic findings in lymphoblastoid cell lines (LCLs) prior to 2009. - PMC - PubMed
    1. Gamazon ER, Zhang W, Konkashbaev A, et al. SCAN: SNP and copy number annotation. Bioinformatics. 2010;26(2):259–262. Useful database that hosts expression quantitative trait loci and copy number variation–quantitative trait loci results in LCLs. - PMC - PubMed
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    1. Wertz IE, Kusam S, Lam C, et al. Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7. Nature. 2011;471(7336):110–114. - PubMed

Websites

    1. The SNP Consortium Database. http://snpdata.cshl.edu.
    1. International HapMap Project. www.hapmap.org.
    1. The 1000 Genomes Project. www.1000genomes.org.
    1. Human Variation Panel dbGaP Access. www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000211.v....
    1. SCAN Database. www.scandb.org.

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