Analysis of Ret Proto-oncogene Mutation in Korean Patients with Medullary Thyroid Carcinomas.
- Author:
Hyung Hoon KIM
1
;
Hyun Jin KIM
;
Yun Jae CHUNG
;
Yong Ki MIN
;
Myung Shik LEE
;
Moon Kyu LEE
;
Kwang Won KIM
;
Chang Seok KI
;
Jong Won KIM
;
Jae Hoon CHUNG
Author Information
1. Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
RET proto-oncogene;
Medullary thyroid carcinoma;
MEN
- MeSH:
Codon;
Diagnosis;
DNA;
Exons;
Female;
Genotype;
Germ-Line Mutation;
Humans;
Korea;
Male;
Multiple Endocrine Neoplasia Type 2a;
Multiple Endocrine Neoplasia Type 2b;
Phenotype;
Polymerase Chain Reaction;
Prevalence;
Proto-Oncogenes*;
Thyroid Gland*;
Thyroid Neoplasms*;
Thyroidectomy
- From:Journal of Korean Society of Endocrinology
2003;18(4):360-370
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Medullary thyroid carcinomas (MTC) have been reported as hereditary in about 25 ~30% of cases. The identification of germline mutation in RET proto-oncogene is important in the diagnosis of hereditary MTC, and occurs in three forms: MEN 2A, MEN 2B and familial MTC (FMTC). To evaluate the prevalence of the relationship of RET proto-oncogene mutation and genotype-phenotype was studied in Korean patients with MTC. METHODS: Genomic DNA was obtained from 29 patients, with MTC, who underwent a total thyroidectomy, between 1997 and 2003, at the Samsung Medical Center. There were 7 male and 22 female patients, with an average age of 39, ranging from 20 to 60 years. Exon 10, 11, 13, 14 and 16 of the RET proto-oncogene were amplified, with specific primers, using PCR. A sequencing analysis was performed on the PCR product using an automatic sequencing analyzer. RESULTS: Nine of the 29 patients (31%) were identified as having RET mutations. The average age of these 9 patients was 33 years, ranging from 20 to 51, with a female to male ratio of 2. Five patients had MEN 2A and one had FMTC, with the other 3 thought to have non-hereditary (sporadic) MTC. The 4 patients with MEN 2A had RET mutations on codon 634 of exon 11 (2 patients, C634R; 2 patients, C634Y) and the other patient on codon 618 of exon 10 (C618R). One patient with FMTC had a mutation on codon 634 (C634W). Three patients with sporadic MTC had RET mutations on codon 634 (2 patients, C634Y; 1 patient, C634S). However, no genotype- phenotype relationship could be found, due to the limited number of patients. CONCLUSION: Thirty-one percent (9/29) of the patients with MTC had RET proto-oncogene mutations. Three-quarters (9/12) of the Korean patients with MEN 2A, including another 7 patients reported in 3 papers in Korea, had RET mutations on codon 634 of exon 11 (4 patients, C634R; 4 patients, C634Y; 1 patient, C634W), but a quarter (3/12) had mutations on codon 618 of exon 10 (2 patients, C618R; 1 patient, C618S). Although no relations could be found between the genotypes and phenotypes, extensive prospective studies will be required to verify this.
