IDENTIFICATION AND CLONING OF 2 OVEREXPRESSED GENES, U21B31/PRAD1 AND EMS1, WITHIN THE AMPLIFIED CHROMOSOME 11Q13 REGION IN HUMAN CARCINOMAS

Amplification of the chromosome 11q13 region is frequently found in human breast cancer and in squamous cell carcinomas of the head and neck, and has been associated with an unfavourable clinical course of disease. The known oncogenes within the amplified 11q13 region, INT2 and HSTF1, are rarely expressed in these tumours, indicating that another, hitherto unidentified, gene or genes confer(s) the biological (prognostic) significance to the amplification of the 11q13 region. To identify the gene or genes, we have constructed a cDNA library from a cell line with an 11q13 amplification and have performed differential cDNA cloning using [P-32]dCTP-labelled cDNAs from human squamous cell carcinoma cell lines with and without an 11q13 amplification. We isolated two cDNA clones, U21B31 and U21C8, which recognize two genes amplified and overexpressed in cell lines harbouring an 11q13 amplification. In breast carcinomas and in squamous cell carcinomas amplification of both the U21B31 and the U21C8 gene was found in most tumours with an amplification of the 11q13 region, despite the large distance between both genes. Sequence analysis of the U21C8 cDNA clone revealed no homology to known genes; we call this gene EMS1. The U21B31 cDNA clone corresponded to the 3' end of the PRAD1 proto-oncogene, recently cloned from a parathyroid adenoma. Both gene products are of interest as potential markers to identify tumours with an 11q13 amplification.