A SERINE PROTEINASE-INHIBITOR LOCUS AT 18Q21.3 CONTAINS A TANDEM DUPLICATION OF THE HUMAN SQUAMOUS-CELL CARCINOMA ANTIGEN GENE

The squamous cell carcinoma antigen (SCCA) is a member of the ovalbumi n family of serine proteinase inhibitors (serpins). A neutral form of the protein is found in normal and some malignant squamous cells, wher eas an acidic form is detected exclusively in tumor cells and in the c irculation of patients with squamous cell tumors. In this report, we d escribe the cloning of the SCCA gene from normal genomic DNA. Surprisi ngly, two genes were found, They were tandemly arrayed and flanked by two other closely related serpins, plasminogen activator inhibitor typ e 2 (PAI2) and maspin at 18q21.3. The genomic structure of the two gen es, SCCA1 and SCCA2, was highly conserved. The predicted amino acid se quences were 92% identical and suggested that the neutral form of the protein was encoded by SCCA1 and the acidic form was encoded by SCCA2. Further characterization of the region should determine whether the d ifferential expression of the SCCA genes plays a causal role in develo pment of more aggressive squamous cell carcinomas.