RET C634*

Prognosis varied in hereditary MTC patients with RET C634 mutations. Our data highlight that the RET C634R mutation was associated with greater tumor aggressiveness in MTC and a poorer disease-specific survival.

These novel findings identify a link between the RET signaling pathway and abnormal osteoblastic bone formation and suggest OPG as a potential biomarker of MTC bone metastases. Patient-derived MTC cells promote osteoblastic lesions in a mouse model.Activating the RET mutation promotes osteoprotegerin.Blocking RET kinase activity inhibits tumor growth and the osteoblastic lesion phenotype.High levels of circulating osteoprotegerin are associated with poor overall survival.

Our results provided the first comprehensive analysis of RET mutations in Vietnamese MTC patients. The most frequent mutation was p.M918T, followed by p.C634R and p.C618R. Mutations in these three exons were linked to specific histopathological features. Information on mutational profiles of patients with MTC will further aid in the development of targeted therapeutics to ensure effective disease management.

This case emphasizes the critical role of genetic testing, continuous monitoring, and a multidisciplinary approach in MEN2A management. The identification of the RET C634R mutation in both the patient and her daughter highlights the need for early intervention and personalized treatment strategies to improve outcomes.

This case emphasizes the important significance of combined analysis of ultrasound, serum biomarkers, cellular pathology, molecular detection, and paraffin pathology in the differential diagnosis of benign and malignant multiple thyroid nodules. It provides a reference for future diagnosis and treatment decisions of multiple thyroid nodules.

From these data, it is clear to see the importance of genetic counseling and RET screening in all first-degree relatives of patients with proven MEN2. The goal should be to subject patients to surgery for prophylactic and not curative purposes, i.e., before the onset of MTC, given the high risk of persistent or recurrent disease also in pediatric/adolescent patients.

This case series highlights the following key message: awareness of the dermatologic findings in MTC/MEN2 patients is essential since lesions such as cutaneous lichen amyloidosis might represent the skin signature of the endocrine condition even before the actual endocrine manifestations. These data add to the limited published reports with respect to this particular presentation, noting the fact that RET-C634 is the most frequent pathogenic variant in MEN2-associated lichen amyloidosis; females are more often affected; the interscapular region is the preferred site; the age of diagnosis might be within the third decade of life, while we reported one of the youngest patients with the lesion. The same RET pathogenic variant is not associated with the same dermatologic features as shown in the vignette. The same RET mutation does not mean that all family members will present the same skin anomaly.

OSMR p. G513D may play a role in modifying the evolutionary processes of CLA in subjects co-harboring RET mutations (further studies are necessary to sustain this aspect). Awareness in CLA-positive patients is essential, including the decision of RET testing in selected cases.

Bypass resistance may be the most frequent mechanism of progression under RETi. A more aggressive histology may arise following RETi and warrants further investigation.

Further structure-based computational studies revealed a significant capability of the most active compounds to the complex RET tyrosine kinase domain. The interesting antiproliferative results supported by in silico predictions suggest that these compounds may represent a starting point for the development of a new series of small heterocyclic molecules for the treatment of MTC.

D898_E901 RET deletion is a gain-of-function mutation and responds to tyrosine kinase inhibitors in MTC. RET Δ898-901 mutant is sensitive to selpercatinib and vandetanib, and acquired resistance to selpercatinib may develop via RET-independent mechanisms.

On the basis of adequate perioperative preparation, surgical resection is the most effective and preferred treatment for this type of disease. Laparoscopic surgery is minimally invasive, safe, and effective by stages. Mutations in the RET proto-oncogene may lead to medullary spongy kidneys in multiple endocrine neoplasia 2.