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Germ-line p53 mutations in 15 families with Li-Fraumeni syndrome.
Am J Hum Genet 1995; 56(3):608-15AJ

Abstract

Germ-line mutations of the tumor-suppressor gene p53 have been observed in some families with the Li-Fraumeni syndrome (LFS), a familial cancer syndrome in which affected relatives develop a diverse set of early-onset malignancies including breast carcinoma, sarcomas, and brain tumors. The analysis of the p53 gene in LFS families has been limited, in most studies to date, to the region between exon 5 and exon 9. In order to determine the frequency and distribution of germ-line p53 mutations in LFS, we sequenced the 10 coding exons of the p53 gene in lymphocytes and fibroblast cell lines derived from 15 families with the syndrome. Germ-line mutations were observed in eight families. Six mutations were missense mutations located between exons 5 and 8. One mutation was a nonsense mutation in exon 6, and one mutation was a splicing mutation in intron 4, generating aberrant shorter p53 RNA(s). In three families, a mutation of the p53 gene was observed in the fibroblast cell line derived from the proband. However, the mutation was not found in affected relatives in two families and in the blood from the one individual, indicating that the mutation probably occurred during cell culture in vitro. In four families, no mutation was observed. This study indicates that germ-line p53 mutations in LFS are mostly located between exons 5 and 8 and that approximately 50% of patients with LFS have no germ-line mutations in the coding region of the p53 gene.(

ABSTRACT

TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Division of Molecular Genetics, Massachusetts General Hospital Cancer Center, Charlestown.No affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

7887414

Citation

Frebourg, T, et al. "Germ-line P53 Mutations in 15 Families With Li-Fraumeni Syndrome." American Journal of Human Genetics, vol. 56, no. 3, 1995, pp. 608-15.
Frebourg T, Barbier N, Yan YX, et al. Germ-line p53 mutations in 15 families with Li-Fraumeni syndrome. Am J Hum Genet. 1995;56(3):608-15.
Frebourg, T., Barbier, N., Yan, Y. X., Garber, J. E., Dreyfus, M., Fraumeni, J., ... Friend, S. H. (1995). Germ-line p53 mutations in 15 families with Li-Fraumeni syndrome. American Journal of Human Genetics, 56(3), pp. 608-15.
Frebourg T, et al. Germ-line P53 Mutations in 15 Families With Li-Fraumeni Syndrome. Am J Hum Genet. 1995;56(3):608-15. PubMed PMID: 7887414.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Germ-line p53 mutations in 15 families with Li-Fraumeni syndrome. AU - Frebourg,T, AU - Barbier,N, AU - Yan,Y X, AU - Garber,J E, AU - Dreyfus,M, AU - Fraumeni,J,Jr AU - Li,F P, AU - Friend,S H, PY - 1995/3/1/pubmed PY - 2001/3/28/medline PY - 1995/3/1/entrez SP - 608 EP - 15 JF - American journal of human genetics JO - Am. J. Hum. Genet. VL - 56 IS - 3 N2 - Germ-line mutations of the tumor-suppressor gene p53 have been observed in some families with the Li-Fraumeni syndrome (LFS), a familial cancer syndrome in which affected relatives develop a diverse set of early-onset malignancies including breast carcinoma, sarcomas, and brain tumors. The analysis of the p53 gene in LFS families has been limited, in most studies to date, to the region between exon 5 and exon 9. In order to determine the frequency and distribution of germ-line p53 mutations in LFS, we sequenced the 10 coding exons of the p53 gene in lymphocytes and fibroblast cell lines derived from 15 families with the syndrome. Germ-line mutations were observed in eight families. Six mutations were missense mutations located between exons 5 and 8. One mutation was a nonsense mutation in exon 6, and one mutation was a splicing mutation in intron 4, generating aberrant shorter p53 RNA(s). In three families, a mutation of the p53 gene was observed in the fibroblast cell line derived from the proband. However, the mutation was not found in affected relatives in two families and in the blood from the one individual, indicating that the mutation probably occurred during cell culture in vitro. In four families, no mutation was observed. This study indicates that germ-line p53 mutations in LFS are mostly located between exons 5 and 8 and that approximately 50% of patients with LFS have no germ-line mutations in the coding region of the p53 gene.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0002-9297 UR - https://www.unboundmedicine.com/medline/citation/7887414/Germ_line_p53_mutations_in_15_families_with_Li_Fraumeni_syndrome_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/7887414/ DB - PRIME DP - Unbound Medicine ER -