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Disease Markers 1986-Dec

Tissue of origin of elevated alpha-fetoprotein in ataxia-telangiectasia.

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T Ishiguro
K Taketa
R A Gatti

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Although only a single gene exists for alpha-fetoprotein (AFP), differential glycosylation generates several different forms and these are associated with different tissues of origin, namely, liver, gastrointestinal tract, and yolk sac. This microheterogeneity of serum AFP was studied in seven patients with ataxia-telangiectasia (AT) in order to determine the tissue of origin of their elevated AFP levels. Concanavalin A (Con A), Lens culinaris agglutinin A (LCA-A), and erythroagglutinating phytohemagglutinin (E-PHA) affinity electrophoresis and antibody-affinity blotting were used to fractionate AFP. It was found that serum AFP in AT patients was composed mainly of Con-A band 2 (AFP-C2), LCA-A band 1 (AFP-L1), and E-PHA band 2 (AFP-P2). This profile of AFP species in AT patients is similar to those seen in neonates and patients with chronic hepatitis, but clearly different from AFP originating in hepatocellular carcinoma, gastric carcinoma, and yolk sac tumour cells. These data are compatible with a hepatic origin for the elevated AFP in AT patients. Since no evidence exists for ongoing liver damage in these patients, we suggest that the AFP gene in the AT liver may be under aberrant transcriptional control, perhaps secondary to a defect of DNA regulatory proteins which are necessary for hepatic maturation.

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