MAPPING OF AMPLIFICATION UNITS IN THE Q13-14 REGION OF CHROMOSOME-12 IN HUMAN SARCOMAS - SOME AMPLICA DO NOT INCLUDE MDM2

Amplification of cellular oncogenes may be important for the developme nt and progression of malignant tumors. In human sarcomas, amplificati on of several genes located to the q13-14 region of chromosome 12 has been reported. Because the mdm2 protein seems to inactivate the tumor suppressor protein p53, a selective growth advantage of 12q13-14 ampli fication has previously been assigned to increased copy number and exp ression of the MDM2 gene. We have analyzed a panel of 98 human sarcoma s of different subtypes to characterize the 12q13-14 amplica and deter mine which of the genes GLI, A2MR, SAS, MDM2, and GADD153 (CHOP) in th is region was most consistently amplified. MDM2 was amplified in 9 of the tumors, SAS in 10, GADD153 in 4, GLI in 2, and A2MR in 2. Amplific ation was, in most cases, associated with increased expression of the corresponding gene. SAS and MDM2 were coamplified in 8 of the tumors, whereas GADD153, GLI, and A2MR were only amplified together with SAS. One liposarcoma showed amplification of MDM2 alone, whereas two osteos arcomas and a rhabdomyosarcoma cell line showed amplification of SAS a nd GADD153 (CHOP) but not MDM2. It is suggested that the selective tar get for these amplica may be an as yet unidentified gene localized bet ween SAS and MDM2.