Alterations affecting tumor suppressor genes, specifically p16INK4 and TP53, have been shown to be involved in the development of human cancer due to their important role in the control of normal cell cycle progression. As the genetic events leading to the development of pediatric osteosarcoma remain partially unclear, we have tested the possibility that a significant number of pediatric osteosarcoma patients harbor mutations in these genes.
PATIENTS AND METHODS
We have analyzed 64 samples (fresh tissues, paraffin embedded biopsies and peripheral blood lymphocytes) corresponding to 38 pediatric osteosarcoma patients. TP53 mutations were analyzed by DGGE (Denaturing Gradient Gel Electrophoresis) analysis of exons 5 through 8. We searched for deletions in the p16INK4 gene by PCR (Polymerase Chain Reaction) analysis and point mutations were screened by means of SSCP (Single Strand Conformation Polymorphisms).
Our analysis showed that 18.4% of the samples harbored mutations in the coding region of TP53 and that 7% had a homozygous deletion of the p16INK4 gene. Our results suggest that p16INK4 deletions may constitute a bad prognostic factor and that TP53 alterations may be correlated, although not statistically, with reduced survival time.
Mutations of the TP53 and deletion of p16INK4 tumor suppressor genes seem to be involved in the development of pediatric osteosarcoma. Moreover, alterations of these genes may constitute a prognostic factor related with poor prognosis or decreased survival time.
CITA DEL ARTÍCULO An Esp Pediatr. 1997 Nov;47(5):478-82
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