a) <i>RET</i> genetic screening is informative in both hereditary and sporadic MTC; b) the prevalence of different mutations varies with V804M being the most frequent; c) the association genotype-phenotype is confirmed; d) by <i>RET</i> screening, some VUS can be found but their pathogenic role must be demonstrated before screening the family.
In the present study, we investigated whether the oncogenic RET mutants RET2A (C634R) and RET2B (M918T) were regulated by LRIG1, and the possible effects of LRIG1 expression in thyroid cancer were investigated in three different clinical cohorts and in a RET2B-driven mouse model of MTC.
In the present study, we investigated whether the oncogenic RET mutants RET2A (C634R) and RET2B (M918T) were regulated by LRIG1, and the possible effects of LRIG1 expression in thyroid cancer were investigated in three different clinical cohorts and in a RET2B-driven mouse model of MTC.
Expression analysis found an increase of RET transcript in p.Cys630=;p.Cys634Arg patient compared with that found in 7 MTCs harboring p.Cys634 mutations.
The RET tyrosine kinase is an important therapeutic target for medullary thyroid cancer (MTC), and drug resistance mutations of RET, particularly V804M and V804L, are a main challenge for the current targeted therapy of MTC based on RET inhibitors.
Based on penetrance analysis in carrier relatives of p.Val804Met-positive cases of MTC, p.Val804Met is currently understood to have high-lifetime penetrance for MTC (87% by age 70), albeit of later onset of MTC than other RET mutations.
The percentage of RET M918T mutation is similar in Mexican MTC patients to other series, although other mutations could be implicated in our population.
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.
This family of 11 individuals with familial MTC type of MEN 2A syndrome demonstrated the moderate risk RET p.Val804Met (protein valine at residue 804 replaced by methionine) genetic mutation, with 2 of the relatives presenting with dermal hyperneury, cutaneous lesions classically described in MEN 2B syndrome, and 1 relative also showing multiple sclerotic fibromas, a cutaneous manifestation of PTEN (phosphatase and tensin homologue) hamartoma-tumor syndrome.
Germline mutations in codon 918 of exon 16 of the RET gene (M918T) are classically associated with multiple endocrine neoplasia type 2B (MEN 2B) with highly aggressive medullary thyroid cancer (MTC), pheochromocytoma and a unique phenotype.
We found higher penetrance of medullary thyroid carcinoma, phaeochromocytoma and hyperparathyroidism (P<0.001, P=0.007 and P<0.001 respectively) in C634R carriers than in C634Y carriers.
MTC samples with the C634 RET mutation exhibited a higher expression of VEGFR3 and KIT than the M918T RET-mutated and non-mutated RET tumor samples (P=0.005 and P=0.007 respectively) and a lower expression of VEGFR1 (P=0.04).
We report a case of an ethnic Chinese girl with MEN2A codon 634 (C634R) mutation, whose operative specimen at prophylactic thyroidectomy at 4 years 8 months showed MTC.
The overall prevalence of RET somatic mutations was lower than expected, and the prevalence of the somatic M918T RET mutation was significantly lower in microMTCs than in larger tumors.
A SNP in exon 13 (L769L) may serve as a modifier in the development of simultaneous MTC and PTC, as well as presentation of MTC, in patients with the RET V804M mutation.