ArticleOrphanet journal of rare diseases2015
The modifier role of RET-G691S polymorphism in hereditary medullary thyroid carcinoma: functional characterization and expression/penetrance studies.
Article in Orphanet journal of rare diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- miR-451a is underexpressed and targets AKT/mTOR pathway in papillary thyroid carcinoma.Oncotarget · 2016Pooled it
- Molecular Characterization of Adult-Type Lower-Grade Glioma (WHO Grade 1-3) with Targeted Next-Generation Sequencing: A Retrospective, Single-Institution Experience.Journal of clinical medicine · 2025Article
- Hereditary Medullary Thyroid Cancer: Genotype-Phenotype Correlation.Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer · 2025Review
- Epidemiology, Clinical Presentation, and Diagnosis of Medullary Thyroid Carcinoma.Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer · 2025Review
- Critically evaluated key points on hereditary medullary thyroid carcinoma.Frontiers in endocrinology · 2024Review
- Molecular Basis and Natural History of Medullary Thyroid Cancer: It is (Almost) All in theCancers · 2023Review
- Article
- Clinical features and signaling effects of RET D631Y variant multiple endocrine neoplasia type 2 (MEN2).The Korean journal of internal medicine · 2022Article
- BRAF Inhibitors Induce Feedback Activation of RAS Pathway in Thyroid Cancer Cells.International journal of molecular sciences · 2021Article
- Spectrum of Germline RET variants identified by targeted sequencing and associated Multiple Endocrine Neoplasia type 2 susceptibility in China.BMC cancer · 2021Article
- The synergy of germline C634Y and V292M RET mutations in a northern Chinese family with multiple endocrine neoplasia type 2A.Journal of cellular and molecular medicine · 2020Article
- State-of-the-Art Strategies for TargetingJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020Review
- Variability in Medullary Thyroid Carcinoma inFrontiers in endocrinology · 2020Article
- cIAP1 regulates the EGFR/Snai2 axis in triple-negative breast cancer cells.Cell death and differentiation · 2018Article
- Association of medullary sponge kidney and hyperparathyroidism with RET G691S/S904S polymorphism: a case report.Journal of medical case reports · 2018Article
- MiR-16 regulates the pro-tumorigenic potential of lung fibroblasts through the inhibition of HGF production in an FGFR-1- and MEK1-dependent manner.Journal of hematology & oncology · 2018Article
- Analysis of Newly Identified and Rare Synonymous Genetic Variants in the RET Gene in Patients with Medullary Thyroid Carcinoma in Polish Population.Endocrine pathology · 2017Article
- RET and EDNRB mutation screening in patients with Hirschsprung disease: Functional studies and its implications for genetic counseling.European journal of human genetics : EJHG · 2016Article
- A patient with MEN1 typical features and MEN2-like features.International journal of endocrine oncology · 2016Article
- Mutational analysis of pulmonary tumours with neuroendocrine features using targeted massive parallel sequencing: a comparison of a neglected tumour group.British journal of cancer · 2015Article
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Authors and funding
11 authors at 3 institutions in 1 country.
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Abstract
backgroundHereditary medullary thyroid carcinoma (MTC) is caused by germ-line gain of function mutations in the RET proto-oncogene, and a phenotypic variability among carriers of the same mutation has been reported. We recently observed this phenomenon in a large familial MTC (FMTC) family carrying the RET-S891A mutation. Among genetic modifiers affecting RET-driven MTC, a role has been hypothesized for RET-G691S non-synonymous polymorphism, though the issue remains controversial. Aim of this study was to define the in vitro contribution of RET-G691S to the oncogenic potential of the RET-S891A, previously shown to harbour low transforming activity.
methodsThe RET-S891A and RET-G691S/S891A mutants were generated by site-directed mutagenesis, transiently transfected in HEK293T cells and stably expressed in NIH3T3 cells. Their oncogenic potential was defined by assessing the migration ability by wound healing assay and the anchorage-independent growth by soft agar assay in NIH3T3 cells stably expressing either the single or the double mutants. Two RET-S891A families were characterised for the presence of RET-G691S.
resultsThe functional studies demonstrated that RET-G691S/S891A double mutant displays a higher oncogenic potential than RET-S891A single mutant, assessed by focus formation and migration ability. Moreover, among the 25 RET-S891A carriers, a trend towards an earlier age of diagnosis was found in the MTC patients harboring RET-S891A in association with RET-G691S.
conclusionsWe demonstrate that the RET-G691S non-synonymous polymorphism enhances in vitro the oncogenic activity of RET-S891A. Moreover, an effect on the phenotype was observed in the RET-G691S/S891A patients, thus suggesting that the analysis of this polymorphism could contribute to the decision on the more appropriate clinical and follow-up management.
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