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The Blood-Based Glycophorin A (GPA) Human In Vivo Somatic Mutation Assay

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Molecular Toxicology Protocols

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1105))

Abstract

The glycophorin A assay concurrently detects and quantifies erythrocytes with allele-loss phenotypes at the autosomal locus responsible for the polymorphic MN blood group. It uses a pair of allele-specific monoclonal antibodies and flow cytometry to efficiently analyze a standard population of five million cells. Two distinct variant phenotypes are detected: simple allele loss and allele loss followed by reduplication of the remaining allele; both are consistent with the mechanisms underlying “loss of heterozygosity” at tumor-suppressor genes. The assay is an intermediate biomarker of biological effect in the somatic mutational model of human cancer and has been applied to populations with a known or suspected genotoxic exposure, to patients with hereditary syndromes causing predisposition to cancer (where the assay has been applied diagnostically), and to patients manifesting cancer as a disease endpoint.

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Acknowledgements

The authors would like to acknowledge Dr. Grant’s colleagues at LLNL who originally conceptualized (Elbert W. Branscomb, William L. Bigbee) and developed (Ronald H. Jensen, Richard G. Langlois) the GPA assay as well as the students (Penelope J. Quintana, Barbara Henry, Reagan K. McLoughlin, Heather Gordish) and technicians (Barbara A. Nisbet, Ann E. Gorvad, Lynn Biedler, Manda K. Welsh, Britt M. Luccy, Jennifer Adair, Julie A. Conte, Christine M. Cerceo, and Khushbu Thumar) who have applied and refined it over the years. They would also like to acknowledge the support of the Pittsburgh Foundation, the Teresa and John Heinz III Foundation, the Richard King Mellon Foundation, and Friends for an Earlier Breast Cancer Test.

Author information

Authors and Affiliations

  1. Public Health Program, Nova Southeastern University, Fort Lauderdale, FL, USA

    Stephen G. Grant

  2. Department of Pharmaceutical Sciences, Nova Southeastern University, Fort Lauderdale, FL, USA

    Nicole T. Myers

Authors
  1. Nicole T. Myers
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  2. Stephen G. Grant
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Corresponding author

Correspondence to Stephen G. Grant .

Editor information

Editors and Affiliations

  1. Occupational Health, University of Pittsburgh Dept. Environmental &, Pittsburgh, Pennsylvania, USA

    Phouthone Keohavong

  2. Dept. of Pharmaceutical Sciences, Nova Southeastern University College of Pharmacy, Fort Lauderdale, Florida, USA

    Stephen G. Grant

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© 2014 Humana Press

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Myers, N.T., Grant, S.G. (2014). The Blood-Based Glycophorin A (GPA) Human In Vivo Somatic Mutation Assay. In: Keohavong, P., Grant, S. (eds) Molecular Toxicology Protocols. Methods in Molecular Biology, vol 1105. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-739-6_18

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  • DOI: https://doi.org/10.1007/978-1-62703-739-6_18

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-738-9

  • Online ISBN: 978-1-62703-739-6

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