The GPA in vivo somatic mutation assay

The glycophorin A (GPA) assay concurrently detects and quantifies two types of erythrocytes with variant 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 analyze a standard population of 5 million cells efficiently. The two phenotypes detected are 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, meaning that it integrates both exposure and biological response. It has been applied to populations with a known or suspected genotoxic exposure, to patients with hereditary syndromes causing predisposition to cancer (in which the assay has begun to be moved from validation mode to application), and to patients manifesting a disease endpoint, i.e., cancer.