Multiple endocrine neoplasia type 2 (MEN 2) and familial medullary thyroid carcinoma (FMTC) are autosomal dominantly inherited cancer syndromes that predispose to C-cell hyperplasia and MTC. MEN 2A and FMTC are caused by mutations in the RET proto-oncogene. We used a multiplex polymerase chain reaction-based assay to screen exons 10, 11, 13, and 14 of RET for mutations in 2 families with FMTC. We correlated mutation status with calcitonin and pathologic studies to determine genotype-phenotype correlations. We identified a mutation in codon 804 in exon 14 (GTG-->ATG; V804M) in both families. An 86-year-old person who was a gene carrier and other individuals over age 70 who were suspected by pedigree analysis to be gene carriers had no overt clinical evidence of MTC. Four of 21 patients who underwent a thyroidectomy also had papillary thyroid cancer. One individual in each family had metastatic MTC at age 30 and 32 years, and all 26 people having thyroidectomies had either MTC or C-cell hyperplasia, leading us to continue to recommend prophylactic thyroidectomy for all identified patients who were gene carriers. Because of active MTC in younger members of these families, including metastases, we have continued to advocate thyroid...Continue Reading
Mucosal ganglioneuromatosis, medullary thyroid carcinoma, and pheochromocytoma: multiple endocrine neoplasia, type 2b
PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas
Familial medullary thyroid carcinoma without associated endocrinopathies: a distinct clinical entity
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Low frequency of germline mutations in the RET proto-oncogene in patients with apparently sporadic medullary thyroid carcinoma
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Germline dinucleotide mutation in codon 883 of the RET proto-oncogene in multiple endocrine neoplasia type 2B without codon 918 mutation
A GTG to ATG novel point mutation at codon 804 in exon 14 of the RET proto-oncogene in two families affected by familial medullary thyroid carcinoma
Synchronous metastatic medullary and papillary thyroid carcinomas in a patient with germline RET mutation: case report, molecular analysis, and implications for pathogenesis
When should thyroidectomy be performed in familial medullary thyroid carcinoma gene carriers with non-cysteine RET mutations?
V804M RET mutation and familial medullary thyroid carcinoma: report of a large family with expression of the disease only in the homozygous gene carriers
Malignant progression from C-cell hyperplasia to medullary thyroid carcinoma in 167 carriers of RET germline mutations
RET proto-oncogene: a review and update of genotype-phenotype correlations in hereditary medullary thyroid cancer and associated endocrine tumors
RET proto-oncogene in Sardinia: V804M is the most frequent mutation and may be associated with FMTC/MEN-2A phenotype
Molecular analysis of the RET proto-oncogene key exons in patients with medullary thyroid carcinoma: a comprehensive study of the Iranian population
The optimal range of RET mutations to be tested: European comments to the guidelines of the American Thyroid Association
Exon 5 of the RET proto-oncogene: a newly detected risk exon for familial medullary thyroid carcinoma, a novel germ-line mutation Gly321Arg
Prevalence by age and predictors of medullary thyroid cancer in patients with lower risk germline RET proto-oncogene mutations
Synchronous occurrence of medullary and papillary carcinoma of the thyroid in a patient with cutaneous melanoma: determination of BRAFV600E in peripheral blood and tissues. Report of a case and review of the literature
Medullary thyroid carcinoma (MTC) and RET proto-oncogene: mutation spectrum in the familial cases and a meta-analysis of studies on the sporadic form
One hundred and seven member family with the rearranged during transfection V804M proto-oncogene mutation presenting with simultaneous medullary and papillary thyroid carcinomas, rare primary hyperparathyroidism, and no pheochromocytomas: Is this a new syndrome-MEN 2C?
One hundred and seven family members with the rearranged during transfection V804M proto-oncogene mutation presenting with simultaneous medullary and papillary thyroid carcinomas, rare primary hyperparathyroidism, and no pheochromocytomas: is this a new syndrome--MEN 2C?
Segregation of the V804L mutation and S836S polymorphism of exon 14 of the RET gene in an extended kindred with familial medullary thyroid cancer
Multiple endocrine neoplasia type 2 RET protooncogene database: repository of MEN2-associated RET sequence variation and reference for genotype/phenotype correlations
Late-onset medullary carcinoma of the thyroid: need for genetic testing and prophylactic thyroidectomy in adult family members
RET proto-oncogene mutations are restricted to codons 634 and 918 in mainland Chinese families with MEN2A and MEN2B
Asymptomatic bilateral adrenal pheochromocytoma in a patient with a germline V804M mutation in the RET proto-oncogene
Experience of prophylactic thyroidectomy in multiple endocrine neoplasia type 2A kindreds with RET codon 804 mutations
RET codon 804 mutations in multiple endocrine neoplasia 2: genotype-phenotype correlations and implications in clinical management
Genetics, diagnosis, and management of medullary thyroid carcinoma and pheochromocytoma/paraganglioma.
Characterization of V804M-mutated RET proto-oncogene associated with familial medullary thyroid cancer, report of the largest Turkish family
Comprehensive assessment of the disputed RET Y791F variant shows no association with medullary thyroid carcinoma susceptibility
RET codon 618 mutations in Saudi families with multiple endocrine neoplasia Type 2A and familial medullary thyroid carcinoma
Difference in development of medullary thyroid carcinoma among carriers of RET mutations in codons 790 and 791
RET codon 634 mutations in multiple endocrine neoplasia type 2: variable clinical features and clinical outcome
Timing and extent of surgery in patients with familial medullary thyroid carcinoma/multiple endocrine neoplasia 2A-related RET mutations not affecting codon 634
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