BACKGROUND: Medulloblastoma is the most common malignant brain tumor of 
childhood. Children who relapse usually die of their disease, which reflects 
resistance to radiation and/or chemotherapy. Improvements in outcome require a 
better understanding of the molecular basis of medulloblastoma growth and 
treatment response. TP73 is a member of the TP53 tumor suppressor gene family 
that has been found to be overexpressed in a variety of tumors and mediates 
apoptotic responses to genotoxic stress. In this study, we assessed expression 
of TP73 RNA species in patient tumor specimens and in medulloblastoma cell 
lines, and manipulated expression of full-length TAp73 and amino-terminal 
truncated DeltaNp73 to assess their effects on growth.
METHODS: We analyzed medulloblastoma samples from thirty-four pediatric patients 
and the established medulloblastoma cell lines, Daoy and D283MED, for expression 
of TP73 RNA including the full-length transcript and the 5'-terminal variants 
that encode the DeltaNp73 isoform, as well as TP53 RNA using quantitative real 
time-RTPCR. Protein expression of TAp73 and DeltaNp73 was quantitated with 
immunoblotting methods. Clinical outcome was analyzed based on TP73 RNA and p53 
protein expression. To determine effects of overexpression or knock-down of 
TAp73 and DeltaNp73 on cell cycle and apoptosis, we analyzed transiently 
transfected medulloblastoma cell lines with flow cytometric and TUNEL methods.
RESULTS: Patient medulloblastoma samples and cell lines expressed full-length 
and 5'-terminal variant TP73 RNA species in 100-fold excess compared to 
non-neoplastic brain controls. Western immunoblot analysis confirmed their 
elevated levels of TAp73 and amino-terminal truncated DeltaNp73 proteins. 
Kaplan-Meier analysis revealed trends toward favorable overall and 
progression-free survival of patients whose tumors display TAp73 RNA 
overexpression. Overexpression of TAp73 or DeltaNp73 induced apoptosis under 
basal growth conditions in vitro and sensitized them to cell death in response 
to chemotherapeutic agents.
CONCLUSION: These results indicate that primary medulloblastomas express 
significant levels of TP73 isoforms, and suggest that they can modulate the 
survival and genotoxic responsiveness of medulloblastomas cells.