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Germline mutations of the p53 tumor-suppressor gene in children and young adults with second malignant neoplasms.
N Engl J Med 1992; 326(20):1309-15NEJM

Abstract

BACKGROUND

Acquired mutations in the p53 tumor-suppressor gene have been detected in several human cancers, including colon, breast, and lung cancer. Inherited mutations (transmitted through the germline) of this gene can underlie the Li-Fraumeni syndrome, a rare familial association of breast cancer in young women, childhood sarcomas, and other malignant neoplasms. We investigated the possibility that p53 mutations in the germline are associated with second primary cancers that arise in children and young adults who would not be considered as belonging to Li-Fraumeni families.

METHODS

Genomic DNA was extracted from the blood leukocytes of 59 children and young adults with a second primary cancer. The polymerase chain reaction, in combination with denaturant-gel electrophoresis and sequencing, was used to identify p53 gene mutations.

RESULTS

Mutations of p53 that changed the predicted amino acid sequence were identified in leukocyte DNA from 4 of the 59 patients (6.8 percent). In three cases, the mutations were identical to ones previously found in the p53 gene. The fourth mutation was the first germline mutation to be identified in exon 9, at codon 325. Analysis of leukocyte DNA from close relatives of three of the patients indicated that the mutations were inherited, but cancer had developed in only one parent at the start of the study.

CONCLUSIONS

These findings identify an important subgroup of young patients with cancer who carry germline mutations in the p53 tumor-suppressor gene but whose family histories are not indicative of the Li-Fraumeni syndrome. The early detection of such mutations would be useful not only in treating these patients, but also in identifying family members who may be at high risk for the development of tumors.

Authors+Show Affiliations

Division of Molecular Genetics, Massachusetts General Hospital Cancer Center, Boston.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

1565144

Citation

Malkin, D, et al. "Germline Mutations of the P53 Tumor-suppressor Gene in Children and Young Adults With Second Malignant Neoplasms." The New England Journal of Medicine, vol. 326, no. 20, 1992, pp. 1309-15.
Malkin D, Jolly KW, Barbier N, et al. Germline mutations of the p53 tumor-suppressor gene in children and young adults with second malignant neoplasms. N Engl J Med. 1992;326(20):1309-15.
Malkin, D., Jolly, K. W., Barbier, N., Look, A. T., Friend, S. H., Gebhardt, M. C., ... Garber, J. (1992). Germline mutations of the p53 tumor-suppressor gene in children and young adults with second malignant neoplasms. The New England Journal of Medicine, 326(20), pp. 1309-15.
Malkin D, et al. Germline Mutations of the P53 Tumor-suppressor Gene in Children and Young Adults With Second Malignant Neoplasms. N Engl J Med. 1992 May 14;326(20):1309-15. PubMed PMID: 1565144.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Germline mutations of the p53 tumor-suppressor gene in children and young adults with second malignant neoplasms. A1 - Malkin,D, AU - Jolly,K W, AU - Barbier,N, AU - Look,A T, AU - Friend,S H, AU - Gebhardt,M C, AU - Andersen,T I, AU - Børresen,A L, AU - Li,F P, AU - Garber,J, PY - 1992/5/14/pubmed PY - 1992/5/14/medline PY - 1992/5/14/entrez SP - 1309 EP - 15 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 326 IS - 20 N2 - BACKGROUND: Acquired mutations in the p53 tumor-suppressor gene have been detected in several human cancers, including colon, breast, and lung cancer. Inherited mutations (transmitted through the germline) of this gene can underlie the Li-Fraumeni syndrome, a rare familial association of breast cancer in young women, childhood sarcomas, and other malignant neoplasms. We investigated the possibility that p53 mutations in the germline are associated with second primary cancers that arise in children and young adults who would not be considered as belonging to Li-Fraumeni families. METHODS: Genomic DNA was extracted from the blood leukocytes of 59 children and young adults with a second primary cancer. The polymerase chain reaction, in combination with denaturant-gel electrophoresis and sequencing, was used to identify p53 gene mutations. RESULTS: Mutations of p53 that changed the predicted amino acid sequence were identified in leukocyte DNA from 4 of the 59 patients (6.8 percent). In three cases, the mutations were identical to ones previously found in the p53 gene. The fourth mutation was the first germline mutation to be identified in exon 9, at codon 325. Analysis of leukocyte DNA from close relatives of three of the patients indicated that the mutations were inherited, but cancer had developed in only one parent at the start of the study. CONCLUSIONS: These findings identify an important subgroup of young patients with cancer who carry germline mutations in the p53 tumor-suppressor gene but whose family histories are not indicative of the Li-Fraumeni syndrome. The early detection of such mutations would be useful not only in treating these patients, but also in identifying family members who may be at high risk for the development of tumors. SN - 0028-4793 UR - https://www.unboundmedicine.com/medline/citation/1565144/Germline_mutations_of_the_p53_tumor_suppressor_gene_in_children_and_young_adults_with_second_malignant_neoplasms_ L2 - http://www.nejm.org/doi/full/10.1056/NEJM199205143262002?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -