Germline Mutations of the APC Gene in Patients with Familial Adenomatous Polyposis-Associated Thyroid Carcinoma: Results from a European Cooperative Study1
| Autor: | Francesco Cetta, M. Gori, M. C. Curia, A. Cama, Sylviane Olschwang, G. Montalto |
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| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_specialty
biology Adenomatous polyposis coli Endocrinology Diabetes and Metabolism Biochemistry (medical) Clinical Biochemistry medicine.disease Biochemistry Germline Stop codon Familial adenomatous polyposis Exon Endocrinology Germline mutation Internal medicine Genotype medicine biology.protein Allele frequency |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 85:286-292 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jcem.85.1.6254 |
| Popis: | Papillary thyroid carcinoma (PTC) is one extracolonic manifestation affecting about 1-2% of patients with familial adenomatous polyposis (FAP). Ninety-seven patients with FAP-associated PTC have previously been reported, including 6 pairs of siblings. During a European collaborative study, 15 patients with FAP-associated PTC were collected. All 15 patients were females. The mean age at thyroidectomy was 24.9 yr (range, 19-39 yr). In 13 subjects, APC germline mutations had been detected; they were at codons 140, 593, 778, 976, 993, 1061 (n = 5), 1105 (n = 1), and 1309 (n = 2), respectively. A review of the literature added 11 other patients with FAP-associated PTC and detection of germline APC mutations; they were at codons 313 (n = 2), 698 (n = 3), 848 (n = 2), 1209 (n = 2), 1061 (n = 1), and 1105 (n = 1), respectively. The latter led to formation of the same stop codon (TAA) at 1125-1126 as the mutation at codon 1061. Therefore, 21 of 24 mutations were in exon 15 in the genomic area usually associated with congenital hypertrophy of the retinal pigment epithelium (CHRPE), i.e. codons 463-1387. Typical CHRPE was found in 17 of 18 affected patients who had specific screening. Interestingly, 22 of the 24 patients had their mutation out of the mutation cluster region (codons 1286-1513), which is currently considered the hot spot mutation area, in particular for extracolonic manifestations of FAP. The difference in the incidence of germline mutations before and after codon 1220 between PTC and non-PTC FAP patients was statistically significant (P |
| Databáze: | OpenAIRE |
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