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Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome.
Nature 1990 Dec 20-27; 348(6303):747-9Nat

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.

Authors+Show Affiliations

Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2259385

Citation

Srivastava, S, et al. "Germ-line Transmission of a Mutated P53 Gene in a Cancer-prone Family With Li-Fraumeni Syndrome." Nature, vol. 348, no. 6303, 1990, pp. 747-9.
Srivastava S, Zou ZQ, Pirollo K, et al. Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature. 1990;348(6303):747-9.
Srivastava, S., Zou, Z. Q., Pirollo, K., Blattner, W., & Chang, E. H. (1990). Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature, 348(6303), pp. 747-9.
Srivastava S, et al. Germ-line Transmission of a Mutated P53 Gene in a Cancer-prone Family With Li-Fraumeni Syndrome. Nature. 1990;348(6303):747-9. PubMed PMID: 2259385.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. AU - Srivastava,S, AU - Zou,Z Q, AU - Pirollo,K, AU - Blattner,W, AU - Chang,E H, PY - 1990/12/20/pubmed PY - 1990/12/20/medline PY - 1990/12/20/entrez SP - 747 EP - 9 JF - Nature JO - Nature VL - 348 IS - 6303 N2 - 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. SN - 0028-0836 UR - https://www.unboundmedicine.com/medline/citation/2259385/Germ_line_transmission_of_a_mutated_p53_gene_in_a_cancer_prone_family_with_Li_Fraumeni_syndrome_ L2 - https://doi.org/10.1038/348747a0 DB - PRIME DP - Unbound Medicine ER -