The molecular basis of Turcot's syndrome
- PMID: 7661930
- DOI: 10.1056/NEJM199503303321302
The molecular basis of Turcot's syndrome
Abstract
Background: Turcot's syndrome is characterized clinically by the concurrence of a primary brain tumor and multiple colorectal adenomas. We attempted to define the syndrome at the molecular level.
Methods: Fourteen families with Turcot's syndrome identified in two registries and the family originally described by Turcot and colleagues were studied. Germ-line mutations in the adenomatous polyposis coli (APC) gene characteristic of familial adenomatous polyposis were evaluated, as well as DNA replication errors and germline mutations in nucleotide mismatch-repair genes characteristic of hereditary nonpolyposis colorectal cancer. In addition, a formal risk analysis for brain tumors in familial adenomatous polyposis was performed with a registry data base.
Results: Genetic abnormalities were identified in 13 of the 14 registry families. Germ-line APC mutations were detected in 10. The predominant brain tumor in these 10 families was medulloblastoma (11 of 14 patients, or 79 percent), and the relative risk of cerebellar medulloblastoma in patients with familial adenomatous polyposis was 92 times that in the general population (95 percent confidence interval, 29 to 269; P < 0.001). In contrast, the type of brain tumor in the other four families was glioblastoma multiforme. The glioblastomas and colorectal tumors in three of these families and in the original family studied by Turcot had replication errors characteristic of hereditary nonpolyposis colorectal cancer. In addition, germ-line mutations in the mismatch-repair genes hMLH1 or hPMS2 were found in two families.
Conclusions: The association between brain tumors and multiple colorectal adenomas can result from two distinct types of germ-line defects: mutation of the APC gene or mutation of a mismatch-repair gene. Molecular diagnosis may contribute to the appropriate care of affected patients.
Comment in
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The APC gene in Turcot's syndrome.N Engl J Med. 1995 Aug 24;333(8):524. doi: 10.1056/NEJM199508243330818. N Engl J Med. 1995. PMID: 7623895 No abstract available.
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The APC gene in Turcot's syndrome.N Engl J Med. 1995 Aug 24;333(8):524. doi: 10.1056/nejm199508243330817. N Engl J Med. 1995. PMID: 7662026 No abstract available.
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Colon-cancer genes and brain tumors.N Engl J Med. 1995 Mar 30;332(13):884-5. doi: 10.1056/NEJM199503303321310. N Engl J Med. 1995. PMID: 7870146 No abstract available.
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Survival of patients with Turcot's syndrome and glioblastoma.N Engl J Med. 1996 Mar 14;334(11):736-7. doi: 10.1056/NEJM199603143341118. N Engl J Med. 1996. PMID: 8594446 No abstract available.
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