Ampli ® cation and over-expression of the MDM 2 gene in human soft tissue tumours

Purpose. Ampli ® cation of genetic sequences on chromosome 12q13 is frequently found in soft tissue tumours. However, for the M DM 2 gene, over-expression of the MDM2 protein has not always been shown to accompany gene ampli® cation, raising the possibility that ampli ® cation of genetic sequences targets alternative genes on chromosome 12q13 for over-expression. To investigate this discrepancy, we have examined 129 soft tissue tumours for ampli® cation of the MDM 2 gene using Southern analysis, and 39 of these tumours were also examined by immunohistochemical staining for MDM2 over-expression. Results. Gene ampli® cation was identi ® ed in 14/114 (12.3%) of the malignant tumours, but was not identi® ed in any of the benign tumours; 21/39 (54%) of the malignant tumours also demonstrated MDM2 over-expression. Within this group the MDM 2 gene was over-expressed in every tumour in which the gene ampli® cation was found, and over-expression in the absence of gene ampli ® cation was also found in an additional 10 tumours. Discussion. These data demonstrate a clear correlation between the presence of M DM2 ampli® cation and MDM2 over-expression, and provide persuasive evidence therefore that the ampli® cation of genetic sequences on chromosome 12q13 in soft tissue sarcomas targets the M DM 2 gene for over-expression. These data also indicate that alternative mechanisms may contribute to MDM2 over-expression within some tumours.