2 GERM-LINE MUTATIONS AFFECTING THE SAME NUCLEOTIDE AT CODON-257 OF P53 GENE, A RARE SITE FOR MUTATIONS

Codon 257 of the p53 gene is an extremely rare target for somatic muta tions (accounting for only two of 1600 published mutations). We report here two constitutional mutations both affecting the second nucleotid e of codon 257. A thymine to adenine transversion resulting in an amin o acid change from leucine to glutamine was found in one proband who d eveloped multiple independent malignant tumors (osteosarcoma, phyllode s tumor, soft-tissue sarcoma). Her mother died of early-onset breast c ancer. In the other case, a deletion resulting in a frameshift in the C-terminal coding region of p53 was found in a woman who was diagnosed with breast cancer at age 34. This woman belongs to a family with fea tures of Li-Fraumeni syndrome. In both cases, the p53 mutations identi fied in the proband was found in other members of the family. Codon 25 7, even if rarely mutated in somatic cells, may thus be an important t arget for germ-line mutations.