An association between viral genes and human oncogenic alterations: The adenovirus E1A induces the Ewing tumor fusion transcript EWS-FLI1

Malignant transformation of human cells requires the accumulation of multip le genetic alterations, such as the activation of oncogenes and loss of fun ction of tumor suppressor genes or those related to genomic instability. Am ong the genetic alterations most frequently found in human tumors are chrom osomal translocations' that may result in the expression of chimeric produc ts with transforming capability or are able to change the expression of onc ogenes. We show here that the adenovirus early region 1A (E1A) gene can ind uce a specific human fusion transcript (EWS-FLI1) that is characteristic of Ewing tumors(2). This fusion transcript was detected by RT-PCR in normal h uman fibroblasts and keratinocytes after expression of the adenovirus E1A g ene, as well as in human cell lines immortalized by adenoviruses. Cloning a nd sequencing of the RT-PCR product showed fusion points between EWS and FL I1 cDNA identical to those detected in Ewing tumors. In addition, we detect ed a chimeric protein by western blot analysis and immunoprecipitation and a t(11,22) by fluorescent in situ hybridization. This association between a single viral gene and a specific human fusion transcript indicates a direc t link between viral genes and chromosome translocations, one of the hallma rks of many human tumors.