Are there low-penetrance TP53 Alleles? evidence from childhood adrenocortical tumors.
Thorncroft, Mary R
James, Louise A
Margison, Geoffrey P
Evans, D Gareth R
Kelsey, Anna M
Birch, Jillian M
AffiliationCancer Research Campaign, Section of Molecular Genetics, Paterson Institute for Cancer Research, Manchester, United Kingdom. firstname.lastname@example.org
MetadataShow full item record
AbstractWe 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.
CitationAre there low-penetrance TP53 Alleles? evidence from childhood adrenocortical tumors. 1999, 65 (4):995-1006 Am. J. Hum. Genet.
JournalAmerican Journal of Human Genetics
- High frequency of germline p53 mutations in childhood adrenocortical cancer.
- Authors: Wagner J, Portwine C, Rabin K, Leclerc JM, Narod SA, Malkin D
- Issue date: 1994 Nov 16
- Germline and somatic mutation analyses in the DNA mismatch repair gene MLH3: Evidence for somatic mutation in colorectal cancers.
- Authors: Lipkin SM, Wang V, Stoler DL, Anderson GR, Kirsch I, Hadley D, Lynch HT, Collins FS
- Issue date: 2001 May
- Li-Fraumeni and Li-Fraumeni-like syndrome among children diagnosed with pediatric cancer in Southern Brazil.
- Authors: Giacomazzi J, Selistre SG, Rossi C, Alemar B, Santos-Silva P, Pereira FS, Netto CB, Cossio SL, Roth DE, Brunetto AL, Zagonel-Oliveira M, Martel-Planche G, Goldim JR, Hainaut P, Camey SA, Ashton-Prolla P
- Issue date: 2013 Dec 15
- Prevalence and functional consequence of TP53 mutations in pediatric adrenocortical carcinoma: a children's oncology group study.
- Authors: Wasserman JD, Novokmet A, Eichler-Jonsson C, Ribeiro RC, Rodriguez-Galindo C, Zambetti GP, Malkin D
- Issue date: 2015 Feb 20
- TP53 germline mutations in adult patients with adrenocortical carcinoma.
- Authors: Herrmann LJ, Heinze B, Fassnacht M, Willenberg HS, Quinkler M, Reisch N, Zink M, Allolio B, Hahner S
- Issue date: 2012 Mar