Exon 5 of the RET proto-oncogene: a newly detected risk exon for familial medullary thyroid carcinoma, a novel germ-line mutation Gly321Arg
Language English Country Italy Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
16419493
DOI
10.1007/bf03345322
PII: 2602
Knihovny.cz E-resources
- MeSH
- Arginine analysis MeSH
- Point Mutation MeSH
- DNA, Neoplasm analysis genetics MeSH
- Adult MeSH
- Exons * MeSH
- Genetic Testing MeSH
- Glycine analysis MeSH
- Codon genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- Carcinoma, Medullary diagnosis genetics surgery MeSH
- Mutation, Missense MeSH
- Thyroid Neoplasms diagnosis genetics surgery MeSH
- Proto-Oncogene Mas MeSH
- Proto-Oncogene Proteins c-ret genetics MeSH
- Proto-Oncogenes * MeSH
- Pedigree MeSH
- Aged MeSH
- Thyroidectomy MeSH
- Germ-Line Mutation * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Arginine MeSH
- DNA, Neoplasm MeSH
- Glycine MeSH
- Codon MeSH
- MAS1 protein, human MeSH Browser
- Proto-Oncogene Mas MeSH
- Proto-Oncogene Proteins c-ret MeSH
- RET protein, human MeSH Browser
Familial medullary thyroid carcinoma (FMTC) is an autosomal dominant inherited disease, characterized by germ-line mutations in the RET proto-oncogene, mainly in exons 10 and 11, but also in exons 13, 14 and 15. Recently, mutations in exons 8 and 16 associated with FMTC were also described. In the herein presented study, single strand conformation polymorphism (SSCP) method for rapid screening of mutations in the RET proto-oncogene and fluorescent sequencing method were used. In one Czech family with FMTC, we have identified a novel missense point mutation of the RET proto-oncogene in exon 5, that results in substitution of arginine by glycine at codon 321 in the cadherin-like domain of ret protein. It seems that this mutation causes FMTC as no other mutation was found in the classical risk exons (10, 11, 13, 14, 15 and 16) of the RET proto-oncogene. The mutation cosegregates with medullary thyroid carcinoma (MTC) or C cell hyperplasia (CCH) in two patients; two other family members are mutation carriers without clinical signs of MTC so far. To improve the diagnosis of FMTC, analysis of exon 5 of the RET proto-oncogene should be considered in families with no identified classical RET mutations.
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