A NOVEL TP53 GERM-LINE MUTATION IDENTIFIED IN A GIRL WITH A PRIMITIVENEUROECTODERMAL TUMOR AND HER FATHER

A search of TP53 mutations was undertaken in a series of 51 pediatric brain tumors. The only germ-line mutation was detected in a 9-year-old girl with a PNET. Her family history was unremarkable for neoplastic disease, except for the paternal grandfather, who died of a gallbladde r carcinoma at an advanced age. The mutation was a thymine deletion at the first base of codon 241, leading to termination codon at position 246 that has not previously been reported. This mutation was found to be inherited from the proband's father, who was healthy at age 40. In the tumoral sample, loss of heterozygosity in several 17p markers was found, the only TP53 allele preserved in the tumor was the mutated on e. The presence of two short tandem repeats and two different palindro mic sequences spanning the deletion lead us to propose the predisposit ion of this region to forming a complex secondary structure during rep lication. Consequently, it could have facilitated the present deletion . Furthermore, six other short deletions affecting-partially or totall y-the region implicated in the folding model that we propose have been described in the literature. These findings confirm that this sequenc e represents a hotspot of deletion in the TP53 gene. (C) Elsevier Scie nce Inc., 1998