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Prevalence and spectrum of germline mutations of the p53 gene among patients with sarcoma.
N Engl J Med 1992; 326(20):1301-8NEJM

Abstract

BACKGROUND

Recent studies have identified germline mutations of the p53 tumor-suppressor gene in families with the Li-Fraumeni syndrome, a rare inherited disorder characterized by a high risk of sarcomas of bone and soft tissue, breast cancer, and other tumors. In this report, we address the possibility that some sporadic sarcomas may be associated with new germline mutations of the p53 gene, which would not be manifested as familial cancer unless the patient survived to reproduce.

METHODS

We studied DNA from peripheral leukocytes of 196 patients with sarcoma and from 200 controls. Of the 196 patients with sarcoma, 15 were selected because they had had multiple primary cancers or had a family history of cancer. The entire coding sequence and splice junctions of the p53 gene were analyzed for mutations.

RESULTS

Eight germline mutations were found, three in patients with no known family history of cancer and five in patients with an unusual personal or family history of cancer. Four mutations caused amino acid substitutions, and four caused stop codons. These mutations were not present in any of the 200 controls.

CONCLUSIONS

New germline mutations of the p53 gene are rare among patients with "sporadic" sarcoma but may be common in patients with sarcoma whose background includes either multiple primary cancers or a family history of cancer. Diverse mutations of this gene were associated with an increased likelihood of cancer; hence, the entire gene should be considered a target for heritable mutation. It appears that the group of patients with cancer who carry germline mutations of the p53 gene is more diverse than is suggested by the clinical definition of the Li-Fraumeni syndrome. The identification of carriers could be of substantial clinical importance.

Authors+Show Affiliations

Massachusetts Eye and Ear Infirmary, Boston 02114.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

1565143

Citation

Toguchida, J, et al. "Prevalence and Spectrum of Germline Mutations of the P53 Gene Among Patients With Sarcoma." The New England Journal of Medicine, vol. 326, no. 20, 1992, pp. 1301-8.
Toguchida J, Yamaguchi T, Dayton SH, et al. Prevalence and spectrum of germline mutations of the p53 gene among patients with sarcoma. N Engl J Med. 1992;326(20):1301-8.
Toguchida, J., Yamaguchi, T., Dayton, S. H., Beauchamp, R. L., Herrera, G. E., Ishizaki, K., ... Sasaki, M. S. (1992). Prevalence and spectrum of germline mutations of the p53 gene among patients with sarcoma. The New England Journal of Medicine, 326(20), pp. 1301-8.
Toguchida J, et al. Prevalence and Spectrum of Germline Mutations of the P53 Gene Among Patients With Sarcoma. N Engl J Med. 1992 May 14;326(20):1301-8. PubMed PMID: 1565143.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prevalence and spectrum of germline mutations of the p53 gene among patients with sarcoma. A1 - Toguchida,J, AU - Yamaguchi,T, AU - Dayton,S H, AU - Beauchamp,R L, AU - Herrera,G E, AU - Ishizaki,K, AU - Yamamuro,T, AU - Meyers,P A, AU - Little,J B, AU - Sasaki,M S, PY - 1992/5/14/pubmed PY - 1992/5/14/medline PY - 1992/5/14/entrez SP - 1301 EP - 8 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 326 IS - 20 N2 - BACKGROUND: Recent studies have identified germline mutations of the p53 tumor-suppressor gene in families with the Li-Fraumeni syndrome, a rare inherited disorder characterized by a high risk of sarcomas of bone and soft tissue, breast cancer, and other tumors. In this report, we address the possibility that some sporadic sarcomas may be associated with new germline mutations of the p53 gene, which would not be manifested as familial cancer unless the patient survived to reproduce. METHODS: We studied DNA from peripheral leukocytes of 196 patients with sarcoma and from 200 controls. Of the 196 patients with sarcoma, 15 were selected because they had had multiple primary cancers or had a family history of cancer. The entire coding sequence and splice junctions of the p53 gene were analyzed for mutations. RESULTS: Eight germline mutations were found, three in patients with no known family history of cancer and five in patients with an unusual personal or family history of cancer. Four mutations caused amino acid substitutions, and four caused stop codons. These mutations were not present in any of the 200 controls. CONCLUSIONS: New germline mutations of the p53 gene are rare among patients with "sporadic" sarcoma but may be common in patients with sarcoma whose background includes either multiple primary cancers or a family history of cancer. Diverse mutations of this gene were associated with an increased likelihood of cancer; hence, the entire gene should be considered a target for heritable mutation. It appears that the group of patients with cancer who carry germline mutations of the p53 gene is more diverse than is suggested by the clinical definition of the Li-Fraumeni syndrome. The identification of carriers could be of substantial clinical importance. SN - 0028-4793 UR - https://www.unboundmedicine.com/medline/citation/1565143/Prevalence_and_spectrum_of_germline_mutations_of_the_p53_gene_among_patients_with_sarcoma_ L2 - http://www.nejm.org/doi/full/10.1056/NEJM199205143262001?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -