CHARACTERIZATION OF A HIGHLY CONSERVED GENE (OS4) AMPLIFIED WITH CDK4IN HUMAN SARCOMAS

Amplification and overexpression of genes involved in growth control o ccur frequently in human Here, we report characterization of the fun l ength OS4 cDNA derived from 12q13-q15 (Su et al., Proc. Natl. Acad. Sc i. USA, 91: 9121-9125, 1994), a region frequently amplified in sarcoma s and brain tumors. This cDNA consists of 4833 base pairs (bp) encodin g an open reading frame (ORF) of 283 amino acids, The ORF predicts a w ater-soluble acidic (pi 5.50) polypeptide with a molecular weight of 3 1 759. Database searches revealed highly significant similarity betwee n OS4 and eight proteins predicted from genomic sequences of Caenorhab ditis elegans, Schizosaccaharomyces pombe, and Saccharomyces cerevisia e. Thus, OS4 defines a novel evolutionarily conserved gene superfamily . Northern and database analyses revealed OS4 transcripts in numerous human tissues demonstrating its ubiquitous expression. We also observe d overexpression of OS4 in three cancer cell lines with amplification of this gene. Furthermore, we detected OS4 amplification in 5/5 primar y sarcomas with known amplification of the closely linked marker CDK4. These results demonstrate that the highly conserved OS4 gene is frequ ently included in the 22q13-q15 amplicon and may contribute to the dev elopment of a subset of sarcomas.