Horizontal transfer of oncogenes by uptake of apoptotic bodies

Tumor formation involves the accumulation of a series of genetic alteration s that are required for malignant growth. In most malignancies, genetic cha nges can be observed at the chromosomal level as losses or gains of whole o r large portions of chromosomes. Here we provide evidence that tumor DNA ma y be horizontally transferred by the uptake of apoptotic bodies. Phagocytos is of apoptotic bodies derived from H-ras(V12)- and human c-myc-transfected rat fibroblasts resulted in loss of contact inhibition in vitro and a tumo rigenic phenotype in vivo. Fluorescence in site hybridization analysis reve aled the presence of rat chromosomes or of rat and mouse fusion chromosomes in the nuclei of the recipient murine cells. The transferred DNA was propa gated, provided that the transferred DNA conferred a selective advantage to the cell and that the phagocytotic host cell was p53-negative. These resul ts suggest that lateral transfer of DNA between eukaryotic cells may result in aneuploidy and the accumulation of genetic changes that are necessary f or tumor formation.