We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
An association between viral genes and human oncogenic alterations: The adenovirus E1A induces the Ewing tumor fusion transcript EWS?FLI1.
- Authors
Sanchez-Prieto, Ricardo; Alava, Enrique de; Palomino, Teresa; Guinea, Juan; Fernandez, Victor; Cebrian, Silvia; LLeonart, Matilde; Cabello, Pablo; Martin, Pilar; Roman, Carlos San; Bornstein, Rafael; Pardo, Javier; Martinez, Ana; Diaz-Espada, Fernando; Barrios, Yve; Cajal, Santiago Ramon y
- Abstract
Malignant transformation of human cells requires the accumulation of multiple genetic alterations, such as the activation of oncogenes and loss of function of tumor suppressor genes or those related to genomic instability. Among the genetic alterations most frequently found in human tumors are chromosomal translocations that may result in the expression of chimeric products with transforming capability or are able to change the expression of oncogenes. We show here that the adenovirus early region lA (E1A) gene can induce a specific human fusion transcript (EWS-FLI1) that is characteristic of Ewing tumors. This fusion transcript was detected by RT-PCR in normal human fibroblasts and keratinocytes after expression of the adenovirus E1A gene, as well as in human cell lines immortalized by adenoviruses. Cloning and sequencing of the RT-PCR product showed fusion points between EWS and FLI1 cDNA identical to those detected in Ewing tumors. In addition, we detected 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 direct link between viral genes and chromosome translocations, one of the hallmarks of many human tumors.
- Subjects
VIRAL genetics; CARCINOGENS; ADENOVIRUSES; EWING'S sarcoma
- Publication
Nature Medicine, 1999, Vol 5, Issue 9, p1076
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/12516