NON-SYNTENIC AMPLIFICATION OF MDM2 AND MYCN IN HUMAN NEUROBLASTOMA

Amplification of the MYCN gene is a well documented genetic alteration of aggressively growing human neuroblastomas. Through cytogenetic stu dies we have identified neuroblastoma cell lines which, in addition to amplified MYCN, carry amplified DNA not harbouring MYCN. In situ hybr idization of biotinylated total genomic DNA to metaphase chromosomes o f normal human lymphocytes by reverse genomic hybridization revealed t he amplified DNA to be derived from chromosome 12 band q13-14, Subsequ ent filter analyses showed a 20- to 40-fold amplification of the MDM2 gene, located at 12q13-14, both in three cell lines and in an original tumor, in addition to amplified MYCN, As the apparent consequence of amplification abundant MDM2 protein was present, a part of which was c omplexed with p53.