ArticleProceedings of the National Academy of Sciences of the United States of America1994
Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
152 citing papers in PubMed, 1 synthesis or guideline pooled it, 597 citations in OpenAlex.
- Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma.Thyroid : official journal of the American Thyroid Association · 2015Guideline
- Trial
- Vandetanib in children and adolescents with multiple endocrine neoplasia type 2B associated medullary thyroid carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Trial
- Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2012Trial
- Hereditary medullary thyroid cancer in Slovenia--genotype-phenotype correlations.Wiener klinische Wochenschrift · 2006Trial
- Mechanism of and research progress on alterations in the RET gene in thyroid cancer (Review).Molecular medicine reports · 2026Review
- Megacolon Associated with Multiple Endocrine Neoplasia Type 2B: A Case Successfully Managed with Ileostomy.Surgical case reports · 2026Article
- Modeling the Effects of Single Nucleotide Polymorphisms (SNPs) on the Structure and Function of the HumanHuman mutation · 2026Article
- Sporadic medullary thyroid carcinoma with a rare RET transmembrane domain mutation (A641R) that responds to selpercatinib.The oncologist · 2025Article
- Mechanisms of resistance to RET-directed therapies.Endocrine-related cancer · 2025Review
- How Tumors Affect Hemodynamics: A Diffusion Study on the Zebrafish Transplantable Model of Medullary Thyroid Carcinoma by Selective Plane Illumination Microscopy.International journal of molecular sciences · 2024Article
- Medullary Thyroid Cancer: Epidemiology and Characteristics According to Data From the Marne-Ardennes Register 1975-2018.Journal of the Endocrine Society · 2024Article
- Well-defined survival outcome disparity across age cutoffs at 45 and 60 for medullary thyroid carcinoma: a long-term retrospective cohort study of 3601 patients.Frontiers in endocrinology · 2024Article
- Molecular Basis and Natural History of Medullary Thyroid Cancer: It is (Almost) All in theCancers · 2023Review
- Article
- Molecular Landscape of Pediatric Thyroid Cancer: A Review.Diagnostics (Basel, Switzerland) · 2022Review
- Fracture Risk in Pediatric Patients With MEN2B.The Journal of clinical endocrinology and metabolism · 2022Article
- Super-enhancer-controlled positive feedback loop BRD4/ERα-RET-ERα promotes ERα-positive breast cancer.Nucleic acids research · 2022Article
- Cystic ovarian teratoma as a novel tumor and growth hormone deficiency as a new condition presenting in Multiple Endocrine Neoplasia type 2B: Case reports and review of the literature.Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia · 2022Review
- RET signaling pathway and RET inhibitors in human cancer.Frontiers in oncology · 2022Review
92 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Multiple endocrine neoplasia type 2B (MEN 2B) is a human cancer syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytomas, mucosal neuromas, ganglioneuromas of the intestinal tract, and skeletal and ophthalmic abnormalities. It appears both as an inherited disorder and as de novo disease. Sequence analysis of germ-line DNA from MEN 2B patients revealed the existence of the same point mutation in the RET protooncogene in 34 unrelated individuals. This sequence difference was not observed in 93 unaffected individuals, including the normal parents of 14 de novo MEN 2B patients. The mutation (ATG-->ACG) results in the replacement of methionine with threonine within the catalytic core region of the tyrosine kinase domain. We propose that this amino acid replacement effects substrate interactions and results in dominant oncogenic activity by the RET protein. Missense mutations in the extracellular ligand-binding domain of the RET protooncogene previously have been associated with two other disorders [MEN 2A and familial MTC (FMTC)] in which MTC is observed. MEN 2B represents the third form of heritable MTC known to be an allele of RET. Alterations in two different functional domains of the putative receptor protein tyrosine kinase are implicated in development of MTC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.