Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li–Fraumeni syndrome View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1990-12

AUTHORS

S Srivastava, Z Q Zou, K Pirollo, W Blattner, E H Chang

ABSTRACT

Tumour suppressor genes, whose usual function seems to be controlling normal cell proliferation, have been implicated in many inherited and sporadic forms of malignancies Much evidence supports the concept of tumour formation by loss-of-function mutations in suppressor genes, as predicted by the two-hit model of Knudson and DeMars. The suppressor gene, p53, is affected in such a manner by numerous mutations, which occur in a variety of human tumours. These mutations usually represent the loss of one allele and the substitution of a single base in the other. We have now analysed the p53 gene in a family affected by Li-Fraumeni syndrome, a rare autosomal dominant syndrome characterized by the occurrence of diverse mesenchymal and epithelial neoplasms at multiple sites. In some instances the neoplasms seem to be related to exposure to carcinogens, including ionizing radiation. The Li-Fraumeni family that we studied had noncancerous skin fibroblasts (NSF) with an unusual radiation-resistant phenotype. DNA derived from the NSF cells of four family members, spanning two generations, had the same point mutation in codon 245 (GGC----GAC) of the p53 gene. This mutation leads to substitution of aspartic acid for glycine in one of the regions identified as a frequent target of point mutations in p53. The NSF cell lines with the mutation also retained the normal p53 allele. This inherited p53 mutation may predispose the members of this family to increased susceptibility to cancer. More... »

PAGES

747-749

Journal

TITLE

Nature

ISSUE

6303

VOLUME

348

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/348747a0

DOI

http://dx.doi.org/10.1038/348747a0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1034283595

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/2259385


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