A constitutional de novo mutation in exon 8 of the p53 gene in a patient with multiple primary malignancies.

摘要: We report a constitutional point mutation of codon 278 in exon 8 the TP53 gene that has not yet been described as germ-line mutation. A 52-year-old female developed multiple primary malignancies (liposarcoma, breast cancer, malignant histiocytoma, occult adenocarcinoma). The found her tumour and peripheral blood lymphocyte DNA is cytosine to thymine transition at second position resulting an amino acid exchange from proline leucine DNA-binding domain. Evaluation patient's family revealed both sons were affected by same Although mother had died already, we able demonstrate polymorphic microsatellite analysis defective allele originated maternal side. As four brothers one sister inherited allele, which however was wild type, show must have occurred germ cells it may therefore be called de novo. This explains lack high cancer incidence history. All tumours tested showed positive immunohistochemical staining for p53. Loss heterozygosity five seven tumours, showing chromosome 17 monosomy.