(3) The single-nucleotide polymorphisms (SNP) G691S in exon 11 (rs1799939), S904S in exon 15 (rs1800863), and rs2075912 and rs2565200 in the 3'-untranslated region of the RET proto-oncogene are in complete linkage disequilibrium (D' = 1, r2 = 1); no correlation of these SNP and MTC was observed in this pedigree.
Forced ATF4 expression decreased survival of MTC cells and blocked the activation of RET downstream signaling pathways (phosphorylated ERK, phosphorylated AKT, and p70S6K).
Moreover, 22 of 56 hereditary MTC (39.3%) were diagnosed preoperatively without FNAC by their high serum calcitonin levels or increased response to calcium stimulation (11 cases each), as well as RET mutation analysis.
The presence of single nucleotide polymorphisms (SNPs) in the REarranged during Transfection (RET) gene has been investigated with regard to their potential role in the development or progression of medullary thyroid cancer or pheochromocytomas (PHEO) in patients with the multiple endocrine neoplasia type 2 (MEN2) syndrome.
A control group consisting of 136 European patients who were thyroidectomised for medullary thyroid carcinoma and devoid of any histologically detectable PTC or follicular-deriving carcinoma was built.
Phaeochromocytoma penetrance and age of diagnosis are highly correlated with MTC aggressiveness based on RET mutation status, with higher penetrance and younger age of diagnosis associated with more aggressive MTC.Penetrance steadily increases with age.
Certain mutations, such as mutations of BRAF in papillary thyroid carcinoma and mutations in RET codons 883, 918, and 928, are associated with an aggressive course in medullary thyroid carcinoma, and affected patients need close surveillance.
Two cases with lung (<i>KIF5B-RET</i>) and medullary thyroid carcinoma (<i>RET</i> M918T) that responded to a vandetanib (multikinase RET inhibitor)-containing regimen are shown.<b>Conclusions:</b><i>RET</i> aberrations were seen in 1.8% of diverse cancers, with most cases harboring actionable, albeit distinct, coexisting alterations.
The percentage of RETM918T mutation is similar in Mexican MTC patients to other series, although other mutations could be implicated in our population.
In the present study, we also showed that the systemic administration of a water soluble NSC311153 analog in a mouse MTC xenograft model inhibited the tumor growth through RET downregulation.
Classical point mutations of RET, BRAF and RAS oncogenes are not shared in papillary and medullary thyroid cancer occurring simultaneously in the same gland.
Genetic testing for the RET gene variants was performed with standard methods in 585 people aged 1-85, including 448 patients with medullary thyroid carcinoma and 131 of their first- and second-degree relatives, as well as six patients suspected of MTC/MEN2.
Variants in the cysteine-rich region of the RET gene, outside of the key cysteine residues, may contribute to the development of MEN2 in a less aggressive manner, with a lower penetrance of MTC.
Oncogenic activation of RET kinase has been found in several neoplastic diseases, like medullary thyroid carcinoma, multiple endocrine neoplasia, papillary thyroid carcinoma, and non-small-cell lung cancer.
Targeted molecular therapies that inhibit RET and other tyrosine kinase receptors involved in angiogenesis have been shown to improve progression-free survival in patients with advanced MTC.
The pattern of tumors in this patient is unusual for either one of the APC- orRASAL1-associated neoplasms and her non-MEN 2-associated MTC contained a RET variant like other sporadic MTCs.
Medullary thyroid cancer (MTC) is a rare tumor arising from the calcitonin-producing parafollicular C cells of the thyroid gland, occurring either sporadically or alternatively in a hereditary form based on germline RET mutations in approximately one-third of cases.