Germ Line p53 Mutations in a Familial Syndrome of Breast Cancer, Sarcomas, and Other Neoplasms

American Association for the Advancement of Science (AAAS) - Tập 250 Số 4985 - Trang 1233-1238 - 1990
David Malkin1,2, Frederick P. Li3,4, Louise C. Strong5,6, Joseph F. Fraumeni7,4, Camille E. Nelson3,2,4, David H. Kim1,2, J Kassel1,2, Magdalena A. Gryka1,2, Farideh Z. Bischoff8, Michael A. Tainsky8, Stephen Friend9,1
1Division of Molecular Genetics, Massachusetts General Hospital Cancer Center, MGH East, Charlestown MA 02129.
2Harvard University
3Clinical Epidemiology Branch, Division of Cancer Etiology, NCI, NIH, Bethesda MD, 20892 and in the Division of Biostatistics and Epidemiology, Dana-Farber Cancer Institute, Boston, MA, 02115.
4NATIONAL INSTITUTES OF HEALTH
5Division of Pediatrics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030.
6Genetics,
7Epidemiology and Biostatistics Program, Division of Cancer Etiology, NCI, NIH, Bethesda MD, 20892.
8Department of Tumor Biology, University of Texas M. D. Anderson Cancer Center, Houston TX, 77030.
9Division of Hematology-Oncology, The Children's Hospital, Dana-Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, Boston MA, 02114.

Tóm tắt

Familial cancer syndromes have helped to define the role of tumor suppressor genes in the development of cancer. The dominantly inherited Li-Fraumeni syndrome (LFS) is of particular interest because of the diversity of childhood and adult tumors that occur in affected individuals. The rarity and high mortality of LFS precluded formal linkage analysis. The alternative approach was to select the most plausible candidate gene. The tumor suppressor gene, p53, was studied because of previous indications that this gene is inactivated in the sporadic (nonfamilial) forms of most cancers that are associated with LFS. Germ line p53 mutations have been detected in all five LFS families analyzed. These mutations do not produce amounts of mutant p53 protein expected to exert a trans-dominant loss of function effect on wild-type p53 protein. The frequency of germ line p53 mutations can now be examined in additional families with LFS, and in other cancer patients and families with clinical features that might be attributed to the mutation.

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American Association for the Advancement of Science (AAAS)

Tập 250 Số 4985

1233-1238

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