MDM2 AMPLIFICATION AND LOSS OF HETEROZYGOSITY AT RB AND P53 GENES - NO SIMULTANEOUS ALTERATIONS IN THE ONCOGENESIS OF LIPOSARCOMAS

Purpose: The present study aimed to investigate the status of alterati ons of the MDM2, Rb and p53 genes in a series of 45 liposarcomas. Furt hermore, the possible correlation with histological and clinical param eters was studied. Methods: MDM2 amplification was examined by non-rad ioactive Southern blot hybridization with a human MDM2 cDNA probe. Mut ations in the p53 gene were screened by polymerase chain reaction/sing le-strand conformation polymorphism analysis and direct sequencing. To study loss of heterozygosity (LOH) at the tumor-suppressor genes Rb a nd p53, we used four polymorphic intragenic Rb markers (introns 1, 17, 20, and 25) and two p53 markers (intron 1 and exon 4). Results: MDM2 amplification was found in 19 of 45 liposarcomas (42.2%). The frequenc y of LOH in Rb and p53 was nearly identical (22%). In 4 of 9 tumors (4 4.4%) with LOH, allelic loss was a concurrent event in both genes. Of 45 liposarcomas, 6 (13.3%) showed p53 mutations. Overall, alterations of the p53/MDM2/Rb pathway occurred in 30 of 45 liposarcomas (66.6%). In contrast to myxoid and pleomorphic variants, well-differentiated li posarcomas were characterized by a high frequency of MDM2 amplificatio n, a lack of LOH of Rh and p53, and p53 mutations. Conclusions: Obviou sly MDM2 amplification and LOH at the Rh and p53 genes do not occur si multaneously in the oncogenesis of liposarcomas, as is the case for MD M2 amplification and p53 gene mutations (with one exception). We sugge st that well-differentiated, myxoid and pleomorphic liposarcomas are c haracterized by a different pattern of molecular alterations.