Disease relevance of MDM2

• Analysis of p53 mutational events and MDM2 amplification in canine soft-tissue sarcomas [1].
• Mdm2 reactivity in reserve-like cells in adenomas showed wide variation, the immunoreactive cells ranging from 4 to 80% [2].
• In contrast to Mdm2 reactivity, each of 14 hyperplastic lesions and 11 adenocarcinomas, and 60 of 65 adenomas (92.3%) failed to show nuclear p53 reactivity [2].
• However, mdm2 gene amplification has only been investigated in a limited number of canine osteosarcomas [1].
• Gene mutations were identified in 6 of 30 (20%) primary tumour cases including MPNST (n=3) leiomysarcoma (n=1), heamangiosarcoma (n=1) and sarcoma (n=1). mdm2 gene amplification was assessed by Southern Blot [1].

High impact information on MDM2

• These results suggest that increased expression of Mdm2 is an early event in circumanal gland tumorigenesis, and may be present in the absence of nuclear p53 protein accumulation [2].
• In 8 of the 9 tumors, mutation of p53 gene or overexpression of MDM2, or both, was detected [3].
• With the exception of one case, a reciprocal relationship between the presence of a p53 mutation and mdm2 gene amplification was demonstrated [1].
• Cloning, sequence analysis and expression of the cDNAs encoding the canine and equine homologues of the mouse double minute 2 (mdm2) proto-oncogene [4].
• The mdm2 oncogene is amplified and overexpressed in a variety of human tumours and the oncogenic potential of MDM2 is partly due to its ability to inactivate tumour suppressor p53 function [4].

Analytical, diagnostic and therapeutic context of MDM2

• In the present communication we describe the cloning, sequence analysis and expression of the complete wildtype canine and equine mdm2 cDNAs [4].

References