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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Complex replication error causes p53 mutation in a Li-Fraumeni family.

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.[1]


  1. Complex replication error causes p53 mutation in a Li-Fraumeni family. Strauss, E.A., Hosler, M.R., Herzog, P., Salhany, K., Louie, R., Felix, C.A. Cancer Res. (1995) [Pubmed]
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