title: Complex replication error causes p53 mutation in a Li-Fraumeni family.
abstract: We demonstrated a germline p53 replication error in two generations of a Li-Fraumeni family affected with liposarcoma, adrenocortical carcinoma, and osteosarcoma. The trinucleotide repeat mutation changed 5'-AGT GTG GTG GTG-3' at codons 215-218 to 5'-AGT TGG TTG GTG GTG-3'. The predicted protein would be elongated by one amino acid (val216-->trp leu) without a change in charge. Detection of p53 in the adrenal tumor by immunostaining suggested that the mutant protein was expressed. Persistence of the mutation in the germline may suggest a defect in DNA repair in the family member first affected. This is the first report where germline transmission of replication-damaged p53 trinucleotide repeats is associated with the Li-Fraumeni syndrome.
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Strauss
authors.forename: M R
authors.initials: MR
authors.lastname: Hosler
authors.forename: P
authors.initials: P
authors.lastname: Herzog
authors.forename: K
authors.initials: K
authors.lastname: Salhany
authors.forename: R
authors.initials: R
authors.lastname: Louie
authors.forename: C A
authors.initials: CA
authors.lastname: Felix
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000378:metabolism; D000328:Adult; D001483:Base Sequence; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007223:Infant; D016864:Li-Fraumeni Syndrome / Q000235:genetics* / Q000378:metabolism; D008080:Liposarcoma / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012516:Osteosarcoma / Q000235:genetics; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D013085:Spermatic Cord; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53