Detection of a human serum DNA-binding protein associated with malignant disease

Human serum DNA-binding proteins were fractionated by DNA-cellulose affinity chromatography. Electrophoretic resolution of these protein fractions allowed the direct comparison of DNA-binding proteins from pools of serum from cancer patients, fetuses, or normal humans. A protein band detected in the fraction eluted by 0.6 M NaCl was elevated in pooled cancer serum, compared to normal or fetal serum. This malignant disease-associated DNA-binding protein (MAD-2) did not react with a variety of antisera directed against specific human serum proteins, blood components, or tumor markers. A chromatography-electrophoresis assay system for MAD-2 that allows the simultaneous determination of 20-30 serum samples was developed. This assay system was used for a preliminary clinical study, which revealed elevated MAD-2 levels in sera from pregnant women and individuals with various carcinomas, compared to levels in sera obtained from normal individuals, patients with nonmalignant diseases, or fetal cord samples.