The blood-based glycophorin A (GPA) human in vivo somatic mutation assay

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.