MDM2 GENE AMPLIFICATION CORRELATES WITH RING CHROMOSOMES IN SOFT-TISSUE TUMORS

The human homolog of the murine double minute type 2 gene (MDM2) has b een cloned and mapped to 12q13-14. The gene presumably functions as a cellular regulator and mediator of TP53 function. Amplification of the MDM2 gene has recently been observed in soft tissue sarcoma and in os teosarcoma. We studied MDM2 amplification in a series of 94 mesenchyma l tumors and found 3-20-fold amplification in 20 tumors: in 10 of 49 m alignant fibrous histiocytomas (MFH), in 1 of 2 pleomorphic liposarcom as, in 6 of 7 atypical lipomas, and in 3 of 12 typical lipomas. Normal hybridization patterns were detected in all 16 myxoid liposarcomas, i n all 3 leiomyosarcomas, and in all 5 leiomyomas studied. The MDM2 amp lification correlated with the presence of marker ring chromosomes; of the 10 MFH with MDM2 amplification, 5 had ring chromosomes, compared to 4 of 39 without MDM2 amplification, and all 9 lipomas with MDM2 amp lification had ring chromosomes, in 5 of the tumors as the sole karyot ypic anomaly. The correlation between ring chromosomes and MDM2 gene a mplification indicates that the marker rings of MFH and of atypical li poma often harbor genetic material derived from chromosome 12. (C) 199 4 Wiley-Liss, Inc.