THE PROTOONCOGENE CHOP GADD153, INVOLVED IN GROWTH ARREST AND DNA-DAMAGE RESPONSE, IS AMPLIFIED IN A SUBSET OF HUMAN SARCOMAS

The C/EBP-homologous transcription factor CHOP (GADD153) is inducible by growth inhibition or DNA damage, and has been shown to be oncogenic ally activated by the specific (12;16) translocation in human myxoid l iposarcoma. We have now found CHOP amplification in two sarcoma cell l ines with previously reported amplification of the nearby GLI gene. Am ong 98 other human sarcomas of various types, CHOP was amplified in a hemangiopericytoma, a liposarcoma, and two osteosarcomas. High constit utive expression levels of CHOP were observed in tumors with gene ampl ification, but also in some other samples. The nearby MDM2 gene, which codes for a protein that may inactivate wild-type p53, has previously been reported to be frequently amplified in sarcoma. In our sarcoma p anel, MDM2 was amplified in 9 cases. MDM2 and CHOP were co-amplified i n two of these, whereas the two osteosarcomas had amplified CHOP but n ot MDM2. CHOP was amplified in both cell lines with GLI amplification, and MDM2 only in one. No mutations in the TP53 gene have been found i n samples with amplification of MDM2. In contrast, the cell line in wh ich CHOP but not MDM2 was amplified had mutated TP53, suggesting that selection of this amplicon was not mediated through p53 inactivation.