Genomes and Genes
multiple endocrine neoplasia type 2a
Summary: A form of multiple endocrine neoplasia characterized by the presence of medullary carcinoma (CARCINOMA, MEDULLARY) of the THYROID GLAND, and usually with the co-occurrence of PHEOCHROMOCYTOMA, producing CALCITONIN and ADRENALINE, respectively. Less frequently, it can occur with hyperplasia or adenoma of the PARATHYROID GLANDS. This disease is due to gain-of-function mutations of the MEN2 gene on CHROMOSOME 10 (Locus: 10q11.2), also known as the RET proto-oncogene that encodes a RECEPTOR PROTEIN-TYROSINE KINASE. It is an autosomal dominant inherited disease.
Publications222 found, 100 shown here
- Diverse phenotypes associated with exon 10 mutations of the RET proto-oncogeneL M Mulligan
Department of Pathology, University of Cambridge, UK
Hum Mol Genet 3:2163-7. 1994..We suggest that specific mutations in cysteine codons 618 and 620 result in MEN 2A or FMTC, but can also predispose to HSCR with low penetrance...
- Guidelines for diagnosis and therapy of MEN type 1 and type 2M L Brandi
Department of Internal Medicine, University of Florence, 50139 Florence, Italy
J Clin Endocrinol Metab 86:5658-71. 2001....
- Risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germline RET mutations located in exon 10Karin Frank-Raue
Endocrine Practice and Molecular Laboratory, Heidelberg, Germany
Hum Mutat 32:51-8. 2011..Our data provide rigorous bases for timing of premorbid diagnosis and personalized treatment/prophylactic procedure decisions depending on specific RET exon 10 codons affected...
- The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysisC Eng
Division of Cancer Epidemiology and Control, Dana Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02115 6084, USA
JAMA 276:1575-9. 1996..The purpose of this study was to establish the relationship between specific mutations and the presence of certain disease features in MEN 2 which could help in clinical decision making...
- RET genetic screening in patients with medullary thyroid cancer and their relatives: experience with 807 individuals at one centerRossella Elisei
Department of Endocrinology, University of Pisa, Via Paradisa 2, 56100 Pisa, Italy
J Clin Endocrinol Metab 92:4725-9. 2007....
- Activation of RET as a dominant transforming gene by germline mutations of MEN2A and MEN2BM Santoro
Centro di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche CNR, Napoli, Italy
Science 267:381-3. 1995..Oncogenic conversion of RET in these neoplastic syndromes establishes germline transmission of dominant transforming genes in human cancer...
- Update multiple endocrine neoplasia type 2Friedhelm Raue
Endocrine Practice, Heidelberg, Germany
Fam Cancer 9:449-57. 2010..MEN 2 gives a unique model for early prevention and cure of cancer and for stratified roles of mutation-based diagnosis of carriers...
- Multiple endocrine neoplasia type 2 syndromes (MEN 2): results from the ItaMEN network analysis on the prevalence of different genotypes and phenotypesCristina Romei
Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy
Eur J Endocrinol 163:301-8. 2010..The prevalence of these rare genetic diseases and their corresponding RET mutations are unknown due to the small size of the study population...
- Pathogenicity of DNA variants and double mutations in multiple endocrine neoplasia type 2 and von Hippel-Lindau syndromeZoran Erlic
Department of Nephrology, Section of Preventive Medicine, Albert Ludwigs University, Freiburg, D 79106 Freiburg, Germany
J Clin Endocrinol Metab 95:308-13. 2010..This observation of coincident DNA variants, both reported as pathogenic, in two known susceptibility genes prompted the question of their pathogenic relevance...
- High penetrance of pheochromocytoma associated with the novel C634Y/Y791F double germline mutation in the RET protooncogeneRodrigo A Toledo
Faculdade de Medicina da Universidade de Sao Paulo, Avenida Dr Arnaldo, 455, 5 degrees andar, Cerqueira Cesar, 012406 903, Sao Paulo, Brazil
J Clin Endocrinol Metab 95:1318-27. 2010....
- RET codon 634 mutations in multiple endocrine neoplasia type 2: variable clinical features and clinical outcomeMarcia K Puñales
Endocrine Division, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035 003, Rio Grande do Sul, Brazil
J Clin Endocrinol Metab 88:2644-9. 2003..001). Our results suggest that specific nucleotide and amino acid exchanges at codon 634 might have a direct impact on tumor aggressiveness in MEN 2A syndrome...
- A new hot spot for mutations in the ret protooncogene causing familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2AI Berndt
Institute for Hormone and Fertility Research, University of Hamburg, Germany
J Clin Endocrinol Metab 83:770-4. 1998One hundred and eighty-one families with multiple endocrine neoplasia type 2A (MEN-2A) or familial medullary thyroid carcinoma (FMTC) have been investigated for mutations in the ret protooncogene in Germany...
- Association of multiple endocrine neoplasia type 2 and Hirschsprung diseaseG Romeo
Department of Pediatric Surgery, Instituto G and University of Genoa Medical School, Italy
J Intern Med 243:515-20. 1998....
- Multiple endocrine neoplasia type 2 RET protooncogene database: repository of MEN2-associated RET sequence variation and reference for genotype/phenotype correlationsRebecca L Margraf
ARUP Institute for Clinical and Experimental Pathology R, Salt Lake City, Utah 84108, USA
Hum Mutat 30:548-56. 2009..The MEN2 RET database (www.arup.utah.edu/database/MEN2/MEN2_welcome.php) will serve as a repository for MEN2-associated RET sequence variation and reference for RET genotype/MEN2 phenotype correlations...
- Modification of multiple endocrine neoplasia 2A phenotype by cell membrane proximity of RET mutations in exon 10Andreas Machens
Department of General, Visceral and Vascular Surgery Pathology, Martin Luther University Halle Wittenberg, Ernst Grube Strasse 40, D 06097 Halle, Germany
Endocr Relat Cancer 16:171-7. 2009..Although limited in numbers, these data suggested that membrane proximity is an important determinant of tumor development in carriers of RET mutations in exon 10...
- Age-related neoplastic risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germ line RET Cys634Trp (TGC>TGG) mutationIoana N Milos
Section of Preventive Medicine, Department of Nephrology, University of Freiburg Medical Centre, Freiburg im Breisgau, Germany
Endocr Relat Cancer 15:1035-41. 2008..These data provide, for the first time, RET C634W-specific neoplastic risk and age-related penetrance profiles. The data may facilitate risk assessment and genetic counseling...
- RET proto-oncogene in the development of human cancerC Eng
Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
J Clin Oncol 17:380-93. 1999..Whether the presence of somatic RET mutation is associated with a poor prognosis is currently being investigated as another tool for molecular medicine...
- Impact of RET proto-oncogene analysis on the clinical management of multiple endocrine neoplasia type 2Sergio Pereira de Almeida Toledo
Genetic Endocrinology Unit (LIM-25, Internal Medicine Department, , , Brazil
Clinics 61:59-70. 2006....
- Polymorphisms G691S/S904S of RET as genetic modifiers of MEN 2AMercedes Robledo
, , Madrid, Spain
Cancer Res 63:1814-7. 2003b>Multiple endocrine neoplasia type 2A (MEN 2A) is associated with specific germ-line missense mutations in the RET proto-oncogene...
- Polymorphisms in RET and its coreceptors and ligands as genetic modifiers of multiple endocrine neoplasia type 2AFabienne Lesueur
Strangeways Research Laboratory, Cancer Research UK Department of Oncology, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK
Cancer Res 66:1177-80. 2006..line missense mutations in the RET proto-oncogene are responsible for the inherited cancer syndrome multiple endocrine neoplasia type 2A (MEN2A)...
- Germ-line mutations in nonsyndromic pheochromocytomaHartmut P H Neumann
Department of Nephrology and Hypertension, Albert Ludwigs University, Freiburg, Germany
N Engl J Med 346:1459-66. 2002....
- The neuron-specific Rai (ShcC) adaptor protein inhibits apoptosis by coupling Ret to the phosphatidylinositol 3-kinase/Akt signaling pathwayGiuliana Pelicci
Department of Experimental Oncology, European Institute of Oncology, 20141 Milan, Italy
Mol Cell Biol 22:7351-63. 2002..Phosphorylated Rai, however, was not found in complexes with Grb2. We propose that Rai potentiates the MAPK and PI3K signaling pathways and regulates Ret-dependent and -independent survival signals...
- Prognostic factors of disease-free survival after thyroidectomy in 170 young patients with a RET germline mutation: a multicenter study of the Groupe Francais d'Etude des Tumeurs EndocrinesV Rohmer
Centre Hospitalier Universitaire Angers, Endocrinologie, Faculte de Medecine, Université Angers, Angers 49933, France
J Clin Endocrinol Metab 96:E509-18. 2011..In hereditary medullary thyroid carcinoma (HMTC), prophylactic surgery is the only curative option, which should be properly defined both in time and extent...
- Pheochromocytoma penetrance varies by RET mutation in MEN 2AFrank J Quayle
Washington University School of Medicine, St Louis, MO 63110, USA
Surgery 142:800-5; discussion 805.e1. 2007The occurrence of pheochromocytoma in multiple endocrine neoplasia type 2A (MEN 2A) carriers varies greatly. This study aims to determine PC expression for specific MEN 2A RET mutations.
- Multiple endocrine neoplasia syndromes, children, Hirschsprung's disease and RETS W Moore
Faculty of Health Sciences, University of Stellenbosch, 7505, Tygerberg, South Africa
Pediatr Surg Int 24:521-30. 2008..The future appears full of promise and the current evaluation of RET-targeting tyrosine kinase and other inhibitors are of considerable interest in the management of these conditions...
- RET genetic screening of sporadic medullary thyroid cancer (MTC) allows the preclinical diagnosis of unsuspected gene carriers and the identification of a relevant percentage of hidden familial MTC (FMTC)C Romei
Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy
Clin Endocrinol (Oxf) 74:241-7. 2011..e. gene carriers) who are unaware of their condition...
- Multiple endocrine neoplasia type 2Nelson Wohllk
Department of Endocrinology, Hospital del Salvador, Universidad de Chile, Chile, Rancagua 835, Providencia Santiago de Chile
Best Pract Res Clin Endocrinol Metab 24:371-87. 2010..Registry-based follow-up should be mandatory including documentation of short- and long-term outcome in order to provide valid data for future counselling of patients with MEN 2...
- [Multiple endocrine neoplasia: a clinical model for applying molecular genetic techniques]N Wohllk
Departamento de Medicina, Hospital del Salvador, Santiago de Chile
Rev Med Chil 128:791-800. 2000..Some cases of sporadic MTC are actually MEN 2A or Familial MTC after c-Ret testing is done, therefore routine application of this test is recommended in all cases of apparent sporadic MTC...
- Increased in vivo phosphorylation of ret tyrosine 1062 is a potential pathogenetic mechanism of multiple endocrine neoplasia type 2BD Salvatore
Centro di Endocrinologia ed Oncologia Sperimentale del CNR, , Italy
Cancer Res 61:1426-31. 2001..The more efficient triggering of these pathways may account for the difference between MEN2A and MEN2B syndromes...
- RET mutation Tyr791Phe: the genetic cause of different diseases derived from neural crestEliska Vaclavikova
Department of Molecular Endocrinology, Institute of Endocrinology, Narodni 8, 116 94, Prague 1, Czech Republic
Endocrine 36:419-24. 2009..A rare case of malignant pheochromocytoma in a patient with the Tyr791Phe mutation is presented. This study shows various clinical characteristics of the frequently discussed Tyr791Phe mutation...
- Familial prevalence and age of RET germline mutations: implications for screeningAndreas Machens
Department of General, Visceral and Vascular Surgery, Martin Luther University Halle Wittenberg, Halle Saale, Germany
Clin Endocrinol (Oxf) 69:81-7. 2008..The current investigation was undertaken to provide such natural history data which are urgently needed to enable factual decision-making about DNA-based screening programmes for RET germline mutations...
- Familial associations in medullary thyroid carcinoma with Hirschsprung disease: the role of the RET-C620 "Janus" genetic variationSam W Moore
Division of Paediatric Surgery, Faculty of Health Sciences, University of Stellenbosch, PO Box 19063, Tygerberg 7505, South Africa
J Pediatr Surg 45:393-6. 2010..Specifically, HSCR-MEN2 cosegregation mostly relates to the cysteine-rich area at the RET-620 (the "Janus gene")...
- RET codon 804 mutations in multiple endocrine neoplasia 2: genotype-phenotype correlations and implications in clinical managementS Mukherjee
Beaumont Cancer Genetics Program, Beaumont Cancer Institute, William Beaumont Hospital, Royal Oak, MI 48073, USA
Clin Genet 79:1-16. 2011..This review summarizes the genotypic and phenotypic characteristics of RET codon 804 mutation, a prototype for the less well-defined non-cysteine RET mutations associated with MEN 2...
- RET-familial medullary thyroid carcinoma mutants Y791F and S891A activate a Src/JAK/STAT3 pathway, independent of glial cell line-derived neurotrophic factorIvan Plaza Menacho
Department of Medical Genetics, University of Groningen, Groningen, The Netherlands
Cancer Res 65:1729-37. 2005..Distinct activating RET mutations cause multiple endocrine neoplasia type 2A (MEN2A), type 2B (MEN2B), and familial medullary thyroid carcinoma (FMTC)...
- RET alternate splicing influences the interaction of activated RET with the SH2 and PTB domains of Shc, and the SH2 domain of Grb2M J Lorenzo
CRC Human Cancer Genetics Research Group, University of Cambridge, Department of Pathology, Cambridge, UK
Oncogene 14:763-71. 1997..In addition, a splice isoform-specific HSCR missense mutation, which does not inactivate the RET kinase activity, decreases the strength of the PTB domain interaction and the level of RET-dependent Shc phosphorylation...
- The clinical spectrum of multiple endocrine neoplasia type 2a caused by the rare intracellular RET mutation S891AKlaus Martin Schulte
Department of Endocrine Surgery, King s College Hospital, Denmark Hill, London SE5 9RS, United Kingdom
J Clin Endocrinol Metab 95:E92-7. 2010..A strong genotype-phenotype correlation results in major implications for the clinical approach. More information on less common mutations is needed to advance specific guidance...
- Multiple endocrine neoplasia type 2: evaluation of the genotype-phenotype relationshipLinwah Yip
Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Arch Surg 138:409-16; discussion 416. 2003..CONCLUSION: Specific RET mutations predict the phenotypic expression of disease and the MTC aggressiveness in patients with MEN 2, guiding the timing of thyroidectomy and screening for pheochromocytoma...
- Allelic imbalance of the mutant and wild-type RET allele in MEN 2A-associated medullary thyroid carcinomaC A Koch
Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Disease NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA
Oncogene 20:7809-11. 2001..Taken together, our results suggest allelic imbalance between mutated and wild-type RET as a possible mechanism for tumor formation in some patients with MEN 2A-related MTC...
- Medullary thyroid carcinoma identified within the first year of life in children with hereditary multiple endocrine neoplasia type 2A (codon 634) and 2BD Zenaty
Paediatric Endocrinology Department, Centre de Référence Maladies Endocriniennes Rares de la Croissance Paediatric Surgery Department Pathology, Assistance Publique Hopitaux de Paris, Robert Debre Hospital, 75019 Paris, France
Eur J Endocrinol 160:807-13. 2009..Early prophylactic thyroidectomy in patients with multiple endocrine neoplasia (MEN) type 2 offers the best chance for a normal life expectancy...
- Prophylactic thyroidectomy in multiple endocrine neoplasia type 2AMichael A Skinner
Department of Surgery, Duke University School of Medicine, Durham, NC, USA
N Engl J Med 353:1105-13. 2005..A longer period of evaluation will be necessary to confirm that they are cured...
- Repair by Src kinase of function-impaired RET with multiple endocrine neoplasia type 2A mutation with substitutions of tyrosines in the COOH-terminal kinase domain for phenylalanineMasashi Kato
Department of Immunology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
Cancer Res 62:2414-22. 2002..Finally, endogenous c-Src was shown to promote Y905 phosphorylation of the Y981F mutant in vivo. These results reveal a novel Src kinase-mediated repair mechanism of otherwise function-impaired mutant RET kinases...
- RET proto-oncogene mutations are restricted to codons 634 and 918 in mainland Chinese families with MEN2A and MEN2BYulin Zhou
Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors, Ruijin Hospital, Jiao Tong University, Shanghai
Clin Endocrinol (Oxf) 67:570-6. 2007..caused by autosomal dominant gain-of-function mutations in the RET proto-oncogene, which includes multiple endocrine neoplasia type 2A (MEN2A), type 2B (MEN 2B), and familial medullary thyroid carcinoma (FMTC)...
- A novel de novo germ-line V292M mutation in the extracellular region of RET in a patient with phaeochromocytoma and medullary thyroid carcinoma: functional characterizationMaria D Castellone
Istituto di Endocrinologia ed Oncologia Sperimentale G Salvatore, CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, L Califano, Universita Federico II, Napoli, Italy
Clin Endocrinol (Oxf) 73:529-34. 2010..In multiple endocrine neoplasia (MEN), rearranged during transfection (RET), gene testing has been extensively exploited to characterize tumour aggressiveness and optimize the diagnostic and clinical management...
- Multiple endocrine neoplasia syndrome: genetic basis for clinical managementTobias Carling
Department of Surgery, Yale University School of Medicine, New Haven, CT 06510, USA
Curr Opin Oncol 17:7-12. 2005..Improved understanding of the molecular and clinical genetics associated with these lesions will likely enhance the diagnosis and treatment of patients with these diseases...
- Genome-wide copy number imbalances identified in familial and sporadic medullary thyroid carcinomaDeborah J Marsh
Cancer Genetics, Kolling Institute of Medical Research, and Pacific Laboratory Medicine Services, Royal North Shore Hospital, St Leonards, New South Wales 2065, Australia
J Clin Endocrinol Metab 88:1866-72. 2003..Chromosomal imbalances in the MTC cell line TT were largely identical to those identified in primary MTC tumors, consolidating its use as a model for studying MTC...
- RET mutations in exons 13 and 14 of FMTC patientsA Bolino
Laboratorio di Genetica Molecolare, Istituto G Gaslini, Genova, Italy
Oncogene 10:2415-9. 1995..tyrosine kinase gene which is responsible for three different inherited cancer syndromes namely multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC) as well as for ..
- Self-association of the transmembrane domain of RET underlies oncogenic activation by MEN2A mutationsS Kjaer
Department of Neuroscience, Division of Molecular Neurobiology, Karolinska Institute, Stockholm, Sweden
Oncogene 25:7086-95. 2006....
- Multiple endocrine neoplasia 2A syndrome: Surgical managementS Simon
Department of Paediatric Surgery, , Erlangen, Germany
J Pediatr Surg 37:897-900. 2002..Further multicenter studies are needed to provide more clinical and prognostic data for less frequent (codon 609, 630, 791, and 891) RET genotypes...
- [Genetic screening of multiple endocrine neoplasia type 2: experience of the USP Endocrine Genetics Unit]Marcelo A C G dos Santos
Unidade de Endocrinologia Genética, Clinica Medica, Faculdade de Medicina, Universidade de Sao Paulo, SP
Arq Bras Endocrinol Metabol 50:7-16. 2006..In 50 typical MEN-2 patients analyzed using both methods, we found no false results suggesting that DGGE is a reliable screening method for RET proto-oncogene mutation analysis...
- Gastrointestinal manifestations of multiple endocrine neoplasia type 2Mark S Cohen
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA
Ann Surg 235:648-54; discussion 654-5. 2002..Patients with MEN 2B have significant gastrointestinal symptoms, but less than a third had surgical intervention. Understanding the clinical course and differences in these patients will improve clinical management...
- Occurrence of pheochromocytoma in a MEN2A family with codon 609 mutation of the RET proto-oncogenePeter Igaz
J Clin Endocrinol Metab 87:2994. 2002
- Molecular advances in medullary thyroid cancer diagnosticsRichard A Hubner
Institute of Cancer Research, Cancer Genetics, 15 Cotswold Road, Sutton, SM2 5NG, United Kingdom
Clin Chim Acta 370:2-8. 2006..Mutation analysis of RET in individuals with MEN2 has identified a number of different mutations, and correlation with cancer biology and clinical outcome has led to tailoring of management according to the mutation detected...
- A novel Czech kindred with familial medullary thyroid carcinoma and Hirschsprung's diseaseSarka Dvorakova
Department of Molecular Endocrinology, Institute of Endocrinology, Prague 11694, Czech Republic
J Pediatr Surg 40:e1-6. 2005..Inactivating germline mutations in the RET proto-oncogene are detected in Hirschsprung's disease (HSCR). Only in a very small number of families are these 2 diseases expressed together...
- Characterization of the largest kindred with MEN2A due to a Cys609Ser RET mutationCaterina Mian
Endocrinology Unit, University of Padua, Padua, Italy
Fam Cancer 8:379-82. 2009..In conclusion, at variance from what already known, in this large kindred the Cys609Ser RET mutation predispose to a scarcely aggressive, highly penetrant MTC and a low penetrance of pheochromocytoma and primary hyperparathyroidism...
- Functional characterization of the MTC-associated germline RET-K666E mutation: evidence of oncogenic potential enhanced by the G691S polymorphismMaria Grazia Borrello
Operative Unit Molecular Mechanisms, Department of Experimental Oncology, IRCCS Istituto Nazionale dei Tumori Foundation, Milan, Italy
Endocr Relat Cancer 18:519-27. 2011..We have demonstrated that, although RET-G691S is not oncogenic per se, it enhances the transforming activity of the RET-K666E mutant, thus suggesting a modifier role for this functional polymorphism...
- [Prophylactic thyroid surgery]A Frilling
Klinik fUr Allgemein, Viszeral und Transplantationschirurgie, Universitatsklinikum Essen
Chirurg 77:6-14. 2006..Although genetic research on hereditary nonmedullary thyroid cancer is still in progress, initial results indicate the need of prophylactic surgical treatment also for this subgroup of thyroid neoplasia...
- RET-mediated gene expression pattern is affected by isoform but not oncogenic mutationJessica G Hickey
Division of Cancer Biology and Genetics, Cancer Research Institute Queen s University, Kingston, ON, Canada, K7L 3N6
Genes Chromosomes Cancer 48:429-40. 2009..Our data suggest that similar transcriptional programs contribute to all forms of MEN 2 but that differences in target gene expression may contribute to developmental pattern differences observed between RET isoforms...
- A novel Val648Ile substitution in RET protooncogene observed in a Cys634Arg multiple endocrine neoplasia type 2A kindred presenting with an adrenocorticotropin-producing pheochromocytomaAdriana B Nunes
Endocrine Genetics Unit, Department of Endocrinology, University of Sao Paulo School of Medicine, 01246 903 Sao Paulo, Brazil
J Clin Endocrinol Metab 87:5658-61. 2002..Both RET variants were present in the father affected with MEN 2A and the unusual ACTH-producing pheochromocytoma. We speculate that the double RET mutation may have modified and contributed to the rare MEN 2A phenotype in the father...
- RET mutation profile and variable clinical manifestations in a family with multiple endocrine neoplasia type 2A and Hirschsprung's diseaseBarbara Pasini
Department of Biomedical Sciences and Advanced Therapies, Section of Endocrinology, University of Ferrara, Via Savonarola 9, I 44100 Ferrara, Italy
Surgery 131:373-81. 2002..Furthermore, we have investigated polymorphic sequence variants of the RET proto-oncogene...
- RET proto-oncogene mutations affecting codon 790/791: A mild form of multiple endocrine neoplasia type 2A syndrome?Oliver Gimm
Department of General, Visceral, and Vascular Surgery, Martin Luther University Halle Wittenberg, Ernst Grube Strasse 40, 06097 Halle, Germany
Surgery 132:952-9; discussion 959. 2002In patients with multiple endocrine neoplasia type 2A syndrome, prophylactic thyroidectomy is generally recommended at the age of 5 to 6 years. Whether this recommendation is justified for exon 13 mutations is unknown.
- Primary hyperparathyroidism as the first clinical manifestation of multiple endocrine neoplasia type 2A in a 5-year-old childPatrícia Künzle Ribeiro Magalhães
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Sao Paulo, Ribeirao Preto, Brazil
Thyroid 21:547-50. 2011Primary hyperparathyroidism occurs in only 10%-30% of patients with multiple endocrine neoplasia type 2A (MEN2A), rarely as the sole clinical manifestation, and is usually diagnosed after the third decade of life.
- Germline RET 634 mutation positive MEN 2A-related C-cell hyperplasias have genetic features consistent with intraepithelial neoplasiaS J Diaz-Cano
Department of Pathology, Tufts University New England Medical Center, Boston, Massachusetts 02111, USA
J Clin Endocrinol Metab 86:3948-57. 2001C-cell hyperplasias are normally multifocal in multiple endocrine neoplasia type 2A. We compared clonality, microsatellite pattern of tumor suppressor genes, and cellular kinetics of C-cell hyperplasia foci in each thyroid lobe...
- Prophylactic thyroidectomy in pediatric carriers of multiple endocrine neoplasia type 2A or familial medullary thyroid carcinoma: mutation in C620 is associated with Hirschsprung's diseaseAndreana Butter
Division of Pediatric Surgery, Sainte Justine Hospital, Montreal, Quebec, Canada, H3T 1C5
J Pediatr Surg 42:203-6. 2007..We reviewed our experience to determine the incidence of medullary thyroid carcinoma with respect to age at surgery, the location of the mutation, and its association with Hirschsprung's disease (HD)...
- Review of multiple endocrine neoplasia type 2A in children: therapeutic results of early thyroidectomy and prognostic value of codon analysisGabor Szinnai
Department of Pediatric Endocrinology, University Children's Hospital, Basel, Switzerland
Pediatrics 111:E132-9. 2003..medullary thyroid carcinoma with persistent or recurrent disease (PRD) in pediatric patients with multiple endocrine neoplasia type 2A (MEN-2A) and second, to evaluate the strength of codon analysis in children with MEN-2A as ..
- Multiple endocrine neoplasia type 2A in two families with the familial medullary thyroid carcinoma associated G533C mutation of the RET proto-oncogeneMelpomeni Peppa
Endocrine Unit, Athens University Medical School, Research Institute and Diabetes Center, Attikon University Hospital, 1 Rimini Street, 12462 Athens, Greece
Eur J Endocrinol 159:767-71. 2008b>Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominant hereditary disorder, associated with a cluster of germline gain-of-function mutations of the RET proto-oncogene (RET), mainly in exons 10-15...
- Consequences of direct genetic testing for germline mutations in the clinical management of families with multiple endocrine neoplasia, type IIH P Neumann
Department of Nephrology and Hypertension, Albert Ludwigs University of Freiburg, Germany
JAMA 274:1149-51. 1995....
- A novel case of multiple endocrine neoplasia type 2A associated with two de novo mutations of the RET protooncogeneA Tessitore
Dipartimento di Biochimica e Biotecnologie Mediche e Ceinge, Centro di Ingegneria Genetica, Universita degli Studi di Napoli Federico II, Italy
J Clin Endocrinol Metab 84:3522-7. 1999We report a novel case of multiple endocrine neoplasia type 2A (MEN 2A) associated with two mutations of the protooncogene RET...
- Acceptable age for prophylactic surgery in children with multiple endocrine neoplasia type 2aT Kahraman
Department of Surgical Oncology Head and Neck Surgery, University Hospital Groningen, Groningen, The Netherlands
Eur J Surg Oncol 29:331-5. 2003..Literature regarding the risk and the extent of early surgical intervention is scarce and the optimum age for surgery is still controversial. To optimize management in these young children we evaluate our experience and results...
- A RET double mutation in the germline of a kindred with FMTCD K Bartsch
Department of Surgery, Philipps University of Marburg, Germany
Exp Clin Endocrinol Diabetes 108:128-32. 2000Activating germline mutations of the RET proto-oncogene are found in more than 90% of families with multiple endocrine neoplasia type 2a (MEN 2a) and familial medullary thyroid carcinoma (FMTC)...
- Germline homozygous mutations at codon 804 in the RET protooncogene in medullary thyroid carcinoma/multiple endocrine neoplasia type 2A patientsF Lesueur
Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, United Kingdom
J Clin Endocrinol Metab 90:3454-7. 2005..The activity and (in the case of somatic mutations) timing of these other genetic alterations in the RET gene may explain the wide clinical variability associated with germline mutations at codon 804...
- Novel germline mutation in the transmembrane region of RET gene close to Cys634Ser mutation associated with MEN 2A syndromeM Poturnajova
Laboratory of Molecular Oncology, Cancer Research Institute SAS, Vlarska 7, 83391 Bratislava, Slovakia
J Mol Med (Berl) 83:287-95. 2005..The observed allelic imbalance in favor of mutated allele in pheochromocytoma corresponded to higher expression of the RET gene. These observations confirm the multifactorial process leading to development of MEN 2A syndrome...
- RET germline mutation in codon 791 in a family representing 3 generations from age 5 to age 70 years: should thyroidectomy be performed?Volker F H Brauer
Department of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany
Endocr Pract 10:5-9. 2004..To describe a kindred with a rare RET germline mutation in codon 791 and discuss potential management strategies...
- Tissue-specific carcinogenesis in transgenic mice expressing the RET proto-oncogene with a multiple endocrine neoplasia type 2A mutationK Kawai
Department of Pathology, Nagoya University School of Medicine, Japan
Cancer Res 60:5254-60. 2000Germ line mutations of the RET proto-oncogene are responsible for the development of multiple endocrine neoplasia type 2A (MEN 2A), an inherited cancer syndrome characterized by medullary thyroid carcinoma, pheochromocytoma, and ..
- Localization of medullary thyroid carcinoma metastasis in a multiple endocrine neoplasia type 2A patient by 6-[18F]-fluorodopamine positron emission tomographyLoukas Gourgiotis
Clinical Endocrinology Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, 20892, USA
J Clin Endocrinol Metab 88:637-41. 2003..Here, we report the case of a 42-yr-old woman with multiple endocrine neoplasia type 2A, in whom biopsy-proven recurrent medullary thyroid cancer (MTC) was detected by 6-[(18)F]..
- Description of the first two seemingly unrelated Greek Cypriot families with a common C618R RET proto-oncogene mutationVassos Neocleous
Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
Genet Test 8:163-8. 2004Germ-line mutations of the RET proto-oncogene cause three different cancer syndromes: multiple endocrine neoplasia type 2A (MEN2A), multiple endocrine neoplasia type 2B, and familial medullary thyroid carcinoma (FMTC)...
- A newly detected mutation of the RET protooncogene in exon 8 as a cause of multiple endocrine neoplasia type 2ASotirios Bethanis
Department of Endocrinology, Athens Polyclinic, Athens, Greece
Hormones (Athens) 6:152-6. 2007b>Multiple endocrine neoplasia type 2A (MEN2A) is a syndrome of familial neoplasias characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperplasia of the parathyroid glands...
- Cellular effects and antitumor activity of RET inhibitor RPI-1 on MEN2A-associated medullary thyroid carcinomaGiuditta Cuccuru
Preclinical Chemotherapy and Pharmacology Unit, and Nuclear Medicine Unit, Istituto Nazionale Tumori, Milan, Italy
J Natl Cancer Inst 96:1006-14. 2004..CONCLUSIONS: Ret oncoproteins represent exploitable targets for therapeutic intervention in MEN2A-associated medullary thyroid carcinoma. The antitumor efficacy and oral bioavailability of RPI-1 support its therapeutic potential...
- Genotype-phenotype based surgical concept of hereditary medullary thyroid carcinomaAndreas Machens
Department of General, Visceral and Vascular Surgery, Martin Luther University Halle Wittenberg, Ernst Grube Str 40, D 06097, Halle Saale, Germany
World J Surg 31:957-68. 2007..A comprehensive appraisal of this body of evidence using evidence-based methodology is pending...
- Surgical treatment of medullary thyroid carcinomaM S Cohen
Department of Surgery, Washington University School of Medicine, St Louis, MO, USA
J Intern Med 253:616-26. 2003..Surgical reoperation or conservative observation are the best available options. Diagnostic laparoscopy for liver evaluation is the most sensitive diagnostic test to detect the presence of distant metastases...
- [Prophylactic thyroidectomy in children who are carriers of a multiple endocrine neoplasia type 2 mutation: description of 20 cases and recommendations based on the literature]J W B de Groot
Afd. Heelkunde en Endocrinologie, Universitair Medisch Centrum Groningen, Postbus 30.001, 9700 RB Groningen
Ned Tijdschr Geneeskd 150:311-8. 2006..After this age, however, the risk of lymph-node metastases increases and, for cases with increased basal or stimulated calcitonin levels, total thyroidectomy with central compartment dissection is indicated...
- Malignant progression from C-cell hyperplasia to medullary thyroid carcinoma in 167 carriers of RET germline mutationsAndreas Machens
Department of General, Visceral and Vascular Surgery, Martin Luther University, Halle Wittenberg, Halle Saale, Germany
Surgery 134:425-31. 2003..The study objective was to investigate the impact of RET genotype on disease progression from C-cell hyperplasia (CCH) to MTC...
- Phenotypic expression of a family with multiple endocrine neoplasia type 2A due to a RET mutation at codon 618S Lindskog
Department of Surgery, Varberg Hospital, Varberg, Sweden
Br J Surg 91:713-8. 2004b>Multiple endocrine neoplasia type 2A (MEN2A) is caused by missense mutations in the RET proto-oncogene on chromosome 10...
- Multiple endocrine neoplasia type 2Mariola Peczkowska
Department of Hypertension, National Institute of Cardiology, Warsaw, Poland
Fam Cancer 4:25-36. 2005..Introduced in recent years and still developing genetic testing of individuals at highest hereditary risk of MEN 2 syndrome holds the possibility of early detection and improved treatment and prognosis...
- Molecular pathogenesis of MEN2-associated tumorsChristian A Koch
University of Leipzig, Philipp Rosenthalstr 27, 04103, Leipzig, Germany
Fam Cancer 4:3-7. 2005..g. codon specific recommendations for prophylactic thyroidectomy) and treatment program, especially for metastatic medullary thyroid carcinoma for which presently no effective therapy other than surgery exists...
- Multiple endocrine neoplasia type 2A: an unusual clinical presentation and association with renal dysplasiaElizabeth McIntyre
Endocrine Unit, Freeman Hospital, Newcastle upon Tyne, UK
Cancer Genet Cytogenet 141:157-9. 2003We report what we believe to be the first case of a patient with multiple endocrine neoplasia type 2A (MEN 2A) and renal dysplasia associated with an RET 634 mutation...
- Amplification and overexpression of mutant RET in multiple endocrine neoplasia type 2-associated medullary thyroid carcinomaSteve C Huang
Molecular Pathogenesis Unit, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA
J Clin Endocrinol Metab 88:459-63. 2003..These findings provide evidence for a third second hit mechanism resulting in overrepresentation and overexpression of mutant RET in MEN 2-associated tumors...
- Somatic VHL gene deletion and point mutation in MEN 2A-associated pheochromocytomaChristian A Koch
Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Disease NICHD, National Institutes of Health NIH, Bethesda, Maryland, MD 20892, USA
Oncogene 21:479-82. 2002..The remaining tumor did show LOH but not mutation of the VHL gene. These results suggest that somatic genetic alterations of the VHL gene may play a role in the tumorigenesis of some MEN 2A-related pheochromocytomas...
- Genetic analysis of RET, GFR alpha 1 and GDNF genes in Spanish families with multiple endocrine neoplasia type 2ALaura Gil
Unidad de Biologia Celular, Centro Nacional de Biologia Fundamental, Instituto de Salud Carlos III, Madrid, Spain
Int J Cancer 99:299-304. 2002b>Multiple endocrine neoplasia type 2A (MEN 2A) is associated with specific germline missense mutations in the RET proto-oncogene...
- Clinical case seminar: in vivo and in vitro characterization of a novel germline RET mutation associated with low-penetrant nonaggressive familial medullary thyroid carcinomaLeonardo D'Aloiso
Unit of Endocrinology and Division of Anatomic Pathology, Istituto di Ricovero e Cura a Carattere Scientifico Csa Sollievo della Sofferenza Hospital, Foggia, Italy
J Clin Endocrinol Metab 91:754-9. 2006..RET mutation analysis provides useful information on the clinical outcome of medullary thyroid carcinomas (MTCs) and the risk of disease in the family members...
- Loss of heterozygosity at the RET protooncogene locus in a case of multiple endocrine neoplasia type 2AL Quadro
Dipartimento di Biochimica e Biotecnologie Mediche and CEINGE Centro di Ingegneria Genetica, , , 80131 Naples, Italy
J Clin Endocrinol Metab 86:239-44. 2001We describe a patient affected by multiple endocrine neoplasia type 2A (MEN 2A) bearing a heterozygous germline mutation (Cys(634)Arg) in exon 11 and an additional somatic mutation of the RET protooncogene...
- Mutations of the RET proto-oncogene in the multiple endocrine neoplasia type 2 syndromes, related sporadic tumours, and hirschsprung diseaseC Eng
Dana Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115 6084, USA
Hum Mutat 9:97-109. 1997..In contrast to MEN 2, approximately 25% of patients with Hirschsprung disease have germline mutations scattered throughout the length of RET...
- Somatic mutations of the RET proto-oncogene are not required for tumor development in multiple endocrine neoplasia type 2 (MEN 2) gene carriersR M Landsvater
Department of Internal Medicine, University Hospital Utrecht, The Netherlands
Cancer Res 56:4853-5. 1996..Thus, RET genes with MEN 2-specific germ line mutations act as dominantly transforming oncogenes in vivo...
- Analysis of RET protooncogene point mutations distinguishes heritable from nonheritable medullary thyroid carcinomasP Komminoth
Division of Cell and Molecular Pathology, University of Zurich, Switzerland
Cancer 76:479-89. 1995..Somatic point mutations in the same gene have been identified in a subset of sporadically occurring medullary thyroid carcinomas...
- [Multiple endocrine neoplasia type 2]Ana Luiza Maia
Servico de Endocrinologia, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS
Arq Bras Endocrinol Metabol 49:725-34. 2005..Progresses related especially to genetic screening and earlier intervention have permitted an improvement in the long-term outcome. However, treatment for disseminated disease is still ineffective...
- [From gene to disease; from the RET gene to multiple endocrine neoplasia types 2A and 2B, sporadic and familial medullary thyroid carcinoma, Hirschsprung disease and papillary thyroid carcinoma]R M Hofstra
Rijksuniversiteit, Disciplinegroep Medische Genetica, Groningen
Ned Tijdschr Geneeskd 145:2217-21. 2001..In particular for MEN2A and FMTC, the clinical management largely depends on the specific mutation found...
- [Lump in the neck: 4 patients with a medullary thyroid carcinoma]M Jansen
afd. Kinderendocrinologie, Universitair Medisch Centrum, Postbus 85.500, 3508 GA Utrecht
Ned Tijdschr Geneeskd 145:2234-41. 2001..The results of DNA tests determine the course of treatment and the need for family testing. In families with a hereditary form, there is a clear genotype-phenotype correlation. Early diagnosis and treatment can improve life expectancy...
- Medullary thyroid carcinoma: nationwide Japanese survey of 634 cases in 1996 and 271 cases in 2002Kaori Kameyama
Division of Diagnostic Pathology, Keio University School of Medicine, Tokyo, Japan
Endocr J 51:453-6. 2004..Genetic testing enables early detection of the disease, which provides patients with the possibility of better outcome...
- [Management of multiple endocrine neoplasia syndrome type 2 families in association with rare germline mutations of the RET proto-oncogene]G Fitze
Klinik für Kinderchirurgie, Universitätsklinikum Carl Gustav Carus der technischen Universität Dresden
Klin Padiatr 216:270-6. 2004..This study describes families with rare noncysteine codon 790/791 mutations and discusses the genotype-phenotype correlation plus the therapeutic options...
- Cost analysis of DNA-based testing in a large Canadian family with multiple endocrine neoplasia type 2D M Gilchrist
Medical Genetics Clinic, University of Alberta, Edmonton, Alberta, Canada
Clin Genet 66:349-52. 2004..As demonstrated by this case, economic costs of genetic diagnostics should take into account the potential saved monies in tests, both molecular and clinical...
- Multiple endocrine neoplasia type 2 and the RET protooncogene: from bedside to bench to bedsideAndreas Machens
Department of General, Visceral and Vascular Surgery, Martin Luther University Halle Wittenberg, Ernst Grube Strasse 40, D 06097 Halle Saale, Germany
Mol Cell Endocrinol 247:34-40. 2006....
- Genetic testing in endocrinology: lessons learned from experience with multiple endocrine neoplasia type 2 (MEN2)Camilo Jimenez
Division of Internal Medicine, Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas M.D. Anderson Cancer Center, Box 433, 1515 Holcombe Blvd, Houston, TX, USA
Growth Horm IGF Res 14:S150-7. 2004....
- Regulation of Receptor Tyrosine KinasesDaniel Donoghue; Fiscal Year: 2005..Mutations in the extracellular juxtamembrane domain of RET cause multiple endocrine neoplasia type 2A (MEN2A) and familial medullary thyroid carcinoma (FMTC), whereas mutations in the intracellular ..
- EDRN: Clinical Epidemiology & Validation CentersHenry Lynch; Fiscal Year: 2007..b. a study to evaluate the acceptability of hypothetical biomarkers among high risk and average risk individuals and primary health care providers. ..
- PHENOTYPIC AND PSYCHOSOCIAL STUDY OF THE L1307K MUTATIONHenry Lynch; Fiscal Year: 2004....
- CORE--MOLECULAR PATHOLOGYRonald Delellis; Fiscal Year: 2002..core abstract not provided ..