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[Multiple endocrine neoplasia type 2A, type 2B and familial medullary thyroid carcinoma syndrome]
T Obara1, T Yamashita, M Kanbe
1Tokyo Women's Medical College, Department of Endocrine Surgery.
Abstract:
Recently, germline mutations in the RET proto-oncogene were found to be associated with multiple endocrine neoplasia (MEN) syndromes, MEN 2A, MEN 2B and Familial medullary thyroid carcinoma (FMTC). In patients with MEN 2A and FMTC different point mutations have been identified in exons 10 and 11 of the cysteine rich regions of RET. Patients with MEN 2B have a single point mutation (ATG to ACG) at codon 918 of RET. Therefore, a direct DNA testing has been developed to provide a highly accurate technique of detecting kindred members who have inherited a specific mutation associated with MEN 2A, MEN 2B or FMTC. In USA and Europe, prophylactic thyroidectomy has been performed on the basis of positive DNA testing, and the presence of a C-cell hyperplasia or a small medullary thyroid carcinoma was confirmed in each patient operated. Through nationwide survey in Japan, 233 patients with MEN 2 syndrome have been identified. They consisted of 180 MEN 2A, 18 MEN 2B, 13 FMTC and 22 unclassified patients. At follow-up, 47% of patients had recurrent medullary thyroid carcinoma and 5.7% of patients died of the disease. Genetic analysis was performed on 15 patients of 6 unrelated families in our series, and the results revealed that germinal mutations of RET as previously reported were also responsible for MEN 2 syndrome in Japanese. DNA analysis and prophylactic thyroidectomy for kindred members at risk for MEN 2 are likely to be beneficial in Japan as well.
Insights
Direct DNA testing for RET proto-oncogene mutations accurately detects hereditary Multiple Endocrine Neoplasia (MEN) syndromes. Early detection and prophylactic thyroidectomy can significantly benefit at-risk individuals in Japan.
Area of Science:
- Endocrinology
- Genetics
- Oncology
Background:
- Germline mutations in the RET proto-oncogene are linked to Multiple Endocrine Neoplasia (MEN) syndromes, including MEN 2A, MEN 2B, and Familial Medullary Thyroid Carcinoma (FMTC).
- Specific RET mutations in exons 10 and 11 are associated with MEN 2A and FMTC, while a distinct mutation at codon 918 characterizes MEN 2B.
Purpose of the Study:
- To investigate the prevalence and genetic basis of MEN 2 syndrome in Japan.
- To evaluate the utility of direct DNA testing and prophylactic thyroidectomy for MEN 2 in the Japanese population.
Main Methods:
- A nationwide survey identified 233 patients with MEN 2 syndrome in Japan.
- Genetic analysis was performed on 15 patients from 6 unrelated families to identify RET proto-oncogene mutations.
- Follow-up data on recurrence and mortality rates were analyzed.
Main Results:
- The study identified 180 cases of MEN 2A, 18 of MEN 2B, and 13 of FMTC.
- Genetic analysis confirmed that germline RET mutations, consistent with previous reports, are responsible for MEN 2 syndrome in Japanese patients.
- A significant proportion of patients (47%) experienced recurrent medullary thyroid carcinoma, and 5.7% died from the disease.
Conclusions:
- Germline RET mutations are a key genetic factor in MEN 2 syndrome among Japanese individuals.
- Direct DNA testing and timely prophylactic thyroidectomy are recommended for at-risk family members in Japan to improve patient outcomes.