J Korean Med Sci.  2010 Feb;25(2):226-229. 10.3346/jkms.2010.25.2.226.

A Korean Family of Familial Medullary Thyroid Cancer with Cys618Ser RET Germline Mutation

• Jung J
• Uchino S
• Lee Y
• Park H

• KMID: 1779251
• DOI: http://doi.org/10.3346/jkms.2010.25.2.226

Abstract

Familial medullary thyroid carcinoma (FMTC) is caused by autosomal dominant gain-of-function mutations in the RET proto-oncogene. An identifiable RET mutation can be detected in about 85% of FMTC families. The majority of germline mutations in FMTC have been found in exons 10 and 11 of the RET proto-oncogene, specifically within the cysteine codons 609, 611, 618, 620, and 634. We screened members of a large Korean family that had a history of FMTC by genetic analyses, and propose a therapeutic approach for managing the disorder. We report a RET mutation in exon10, codon 618 that causes substitution of a cysteine by a serine in the cysteine-rich domain of the RET receptor in a three-generation FMTC family composed of 30 members with 11 carriers. Nine of the gene carriers were clinically affected. The FMTC with cysteine RET mutations found in the Korean population is consistent with the clinical pattern reported worldwide; to date there have been no ethnic differences identified for FMTC. Our results suggest that this genetic profile might be associated with usually aggressive clinical course with regional lymph node metastasis but late onset of MTC.

Keyword

Familial Medullary Thyroid Carcinoma; RET Mutation; Genetic Testing

MeSH Terms

Adolescent
Adult
Aged
Amino Acid Substitution
Carcinoma, Medullary/*genetics/pathology/secondary
Exons
Female
Genetic Predisposition to Disease
Genetic Testing
Genotype
*Germ-Line Mutation
Humans
Male
Middle Aged
Pedigree
Proto-Oncogene Proteins c-ret/*genetics
Republic of Korea
Thyroid Neoplasms/*genetics/pathology
Proto-Oncogene Proteins c-ret

Figure

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  Fig. 1 Pedigree of the family with familial medullary thyroid carcinoma. Circles and squares denote female and male family members, respectively.

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  Fig. 2 The sequence TGC encoding cysteine in the wild-type is changed to the sequence AGC encoding serine in codon 618 on exon 10 of the RET proto-oncogene.

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