Abstract:
:The Li-Fraumeni Syndrome (LFS) is a rare, dominantly inherited syndrome that features high risk of cancers in childhood and early adulthood. Affected families tend to develop bone and soft tissue sarcomas, breast cancers, brain tumors, leukemias, and adrenocortical carcinomas. In some kindreds, the genetic abnormality associated with this cancer phenotype is a heterozygous germline mutation in the p53 tumor suppressor gene. Recently, we identified one patient who presented in early childhood with multiple primary cancers and who harbored three germline p53 alterations (R156H and R267Q on the maternal allele and R290H on the paternal allele). To classify the biologic effects of these alterations, functional properties of each of the p53 mutants were examined using in vitro assays of cellular growth suppression and transcriptional activation. Each amino acid substitution conferred partial or complete loss of wild-type p53 function, but the child completed normal embryonic development. This observation has not been previously reported in a human, but is consistent with observations of normal embryogenesis in p53-deficient mice.
journal_name
Oncogenejournal_title
Oncogeneauthors
Quesnel S,Verselis S,Portwine C,Garber J,White M,Feunteun J,Malkin D,Li FPdoi
10.1038/sj.onc.1202783subject
Has Abstractpub_date
1999-07-08 00:00:00pages
3970-8issue
27eissn
0950-9232issn
1476-5594journal_volume
18pub_type
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