Are there low-penetrance TP53 Alleles? evidence from childhood adrenocortical tumors.
Authors
Varley, JenniferMcGown, Gail
Thorncroft, Mary R
James, Louise A
Margison, Geoffrey P
Forster, Gill
Evans, D Gareth R
Harris, Martin
Kelsey, Anna M
Birch, Jillian M
Affiliation
Cancer Research Campaign, Section of Molecular Genetics, Paterson Institute for Cancer Research, Manchester, United Kingdom. jvarley@picr.man.ac.ukIssue Date
1999-10
Metadata
Show full item recordAbstract
We have analyzed a panel of 14 cases of childhood adrenocortical tumors unselected for family history and have identified germline TP53 mutations in >80%, making this the highest known incidence of a germline mutation in a tumor-suppressor gene in any cancer. The spectrum of germline TP53 mutations detected is remarkably limited. Analysis of tumor tissue for loss of constitutional heterozygosity, with respect to the germline mutant allele and the occurrence of other somatic TP53 mutations, indicates complex sequences of genetic events in a number of tumors. None of the families had cancer histories that conformed to the criteria for Li-Fraumeni syndrome, but, in some families, we were able to demonstrate that the mutation had been inherited. In these families there were gene carriers unaffected in their 40s and 50s, and there were others with relatively late-onset cancers. These data provide evidence that certain TP53 alleles confer relatively low penetrance for predisposition to the development of cancer, and they imply that deleterious TP53 mutations may be more frequent in the population than has been estimated previously. Our findings have considerable implications for the clinical management of children with andrenocortical tumors and their parents, in terms of both genetic testing and the early detection and treatment of tumors.Citation
Are there low-penetrance TP53 Alleles? evidence from childhood adrenocortical tumors. 1999, 65 (4):995-1006 Am. J. Hum. Genet.Journal
American Journal of Human GeneticsDOI
10.1086/302575PubMed ID
10486318Type
ArticleLanguage
enISSN
0002-9297ae974a485f413a2113503eed53cd6c53
10.1086/302575