Related Experiment Videos
RET protooncogene mutations in patients with apparently sporadic medullary thyroid carcinoma
1Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Abstract:
We examined RET protooncogene mutations in sporadic medullary thyroid carcinoma (MTC), using polymerase chain reaction (PCR)-based sequencing. DNA was extracted from tumor tissue and peripheral blood leukocytes of seven unrelated individuals with apparently sporadic MTC. Oligonucleotide primers were selected to amplify exons 10, 11, 13, 15, and 16 of the RET protooncogene, to examine the sequences of codons 609, 611, 618, and 620 of exon 10, codon 634 of exon 11, codon 768 of exon 13, codon 883 of exon 15, and codon 918 of exon 16. Direct DNA sequencing from PCR products was then performed. The results showed that one patient had a somatic mutation at codon 918 (ATG-->ACG), causing a Met-->Thr substitution. One patient had a de novo germline mutation at codon 634 (TGC-->CGC), causing a Cys-->Arg substitution. Another patient had a germline mutation at codon 634 (TGC-->TTC), causing a Cys-->Phe substitution. In the remaining four cases, no RET mutations were found. Unexpectedly, two offspring of the patient (a female) with a germline mutation at codon 634 (TGC-->TTC) harbored homozygous alleles for the mutation; because the father did not carry this mutation, the other affected allele was suspected to have resulted from a de novo germline mutation of paternal origin. One of these offspring was subsequently diagnosed as having MTC. Our findings suggest that all patients with apparently sporadic MTC should be screened for the RET protooncogene by molecular analysis to detect occult or de novo multiple endocrine neoplasia 2 (MEN 2) or familial MTC. This would allow early treatment of affected family members.
Insights
RET protooncogene mutations are key in sporadic medullary thyroid carcinoma (MTC). Molecular screening of RET is crucial for detecting occult multiple endocrine neoplasia 2 (MEN 2) or familial MTC, enabling early intervention.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Medullary thyroid carcinoma (MTC) can be sporadic or familial.
- The RET protooncogene is implicated in MTC development.
- Identifying RET mutations aids in diagnosing familial MTC and multiple endocrine neoplasia 2 (MEN 2).
Purpose of the Study:
- To investigate RET protooncogene mutations in sporadic medullary thyroid carcinoma (MTC).
- To determine the frequency and types of RET mutations in MTC patients.
- To assess the utility of molecular screening for RET mutations in sporadic MTC cases.
Main Methods:
- DNA extraction from tumor tissue and peripheral blood leukocytes.
- Polymerase chain reaction (PCR) amplification of key RET protooncogene exons (10, 11, 13, 15, 16).
- Direct DNA sequencing of PCR products to identify mutations.
Main Results:
- One somatic mutation (Met-->Thr at codon 918) and two de novo germline mutations (Cys-->Arg at codon 634 and Cys-->Phe at codon 634) were identified.
- No RET mutations were found in four cases.
- Homozygous alleles for a germline mutation were observed in offspring, suggesting a de novo paternal mutation, with one offspring diagnosed with MTC.
Conclusions:
- Molecular analysis of the RET protooncogene is essential for patients with apparently sporadic MTC.
- Screening can detect occult or de novo MEN 2 or familial MTC.
- Early detection through RET mutation screening facilitates timely treatment for affected individuals and families.