multiple endocrine neoplasia type 2a

Summary

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.

Top Publications

  1. Gourgiotis L, Sarlis N, Reynolds J, VanWaes C, Merino M, Pacak K. Localization of medullary thyroid carcinoma metastasis in a multiple endocrine neoplasia type 2A patient by 6-[18F]-fluorodopamine positron emission tomography. J Clin Endocrinol Metab. 2003;88:637-41 pubmed
    ..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]..
  2. Puñales M, Graf H, Gross J, Maia A. RET codon 634 mutations in multiple endocrine neoplasia type 2: variable clinical features and clinical outcome. J Clin Endocrinol Metab. 2003;88:2644-9 pubmed
    ..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...
  3. Poturnajova M, Altanerova V, Kostalova L, Breza J, Altaner C. Novel germline mutation in the transmembrane region of RET gene close to Cys634Ser mutation associated with MEN 2A syndrome. J Mol Med (Berl). 2005;83:287-95 pubmed
    ..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...
  4. Santos M, Nunes A, Abelin N, Ezabella M, Toledo R, Lourenço D, et al. [Genetic screening of multiple endocrine neoplasia type 2: experience of the USP Endocrine Genetics Unit]. Arq Bras Endocrinol Metabol. 2006;50:7-16 pubmed
    ..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...
  5. de Groot J, Links T, Rouwe C, van der Wal J, Hofstra R, Plukker J. [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]. Ned Tijdschr Geneeskd. 2006;150:311-8 pubmed
    ..Evaluation of treatment of children who are proven carriers of a multiple endocrine neoplasia type 2 (MEN 2)-associated rearranged during transfection (RET) gene mutation...
  6. Tömböl Z, Eder K, Kovacs A, Szabó P, Kulka J, Liko I, et al. MicroRNA expression profiling in benign (sporadic and hereditary) and recurring adrenal pheochromocytomas. Mod Pathol. 2010;23:1583-95 pubmed publisher
    ..MicroRNA expression patterns differ between various sporadic, hereditary and recurring tumors and miR-1225-3p may be useful for identifying recurring pheochromocytomas...
  7. Peppa M, Boutati E, Kamakari S, Pikounis V, Peros G, Panayiotides I, et al. Multiple endocrine neoplasia type 2A in two families with the familial medullary thyroid carcinoma associated G533C mutation of the RET proto-oncogene. Eur J Endocrinol. 2008;159:767-71 pubmed publisher
    b>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...
  8. Magalhães P, Antonini S, de Paula F, De Freitas L, Maciel L. Primary hyperparathyroidism as the first clinical manifestation of multiple endocrine neoplasia type 2A in a 5-year-old child. Thyroid. 2011;21:547-50 pubmed publisher
    Primary 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.
  9. Lindskog S, Nilsson O, Jansson S, Nilsson B, Illerskog A, Ysander L, et al. Phenotypic expression of a family with multiple endocrine neoplasia type 2A due to a RET mutation at codon 618. Br J Surg. 2004;91:713-8 pubmed
    b>Multiple endocrine neoplasia type 2A (MEN2A) is caused by missense mutations in the RET proto-oncogene on chromosome 10...

More Information

Publications62

  1. Moline J, Eng C. Multiple endocrine neoplasia type 2: an overview. Genet Med. 2011;13:755-64 pubmed publisher
    ..b>Multiple endocrine neoplasia type 2A, familial medullary thyroid carcinoma, and multiple endocrine neoplasia type 2B are collectively ..
  2. Lau G, Lang B, Lo C, Tso A, Garcia Barcelo M, Tam P, et al. Prophylactic thyroidectomy in ethnic Chinese patients with multiple endocrine neoplasia type 2A syndrome after the introduction of genetic testing. Hong Kong Med J. 2009;15:326-31 pubmed
    ..To evaluate the impact of genetic testing in the management of familial multiple endocrine neoplasia 2A patients...
  3. Machens A, Holzhausen H, Thanh P, Dralle H. Malignant progression from C-cell hyperplasia to medullary thyroid carcinoma in 167 carriers of RET germline mutations. Surgery. 2003;134:425-31 pubmed
    ..The study objective was to investigate the impact of RET genotype on disease progression from C-cell hyperplasia (CCH) to MTC...
  4. Romei C, Mariotti S, Fugazzola L, Taccaliti A, Pacini F, Opocher G, et al. Multiple endocrine neoplasia type 2 syndromes (MEN 2): results from the ItaMEN network analysis on the prevalence of different genotypes and phenotypes. Eur J Endocrinol. 2010;163:301-8 pubmed publisher
    ..The prevalence of these rare genetic diseases and their corresponding RET mutations are unknown due to the small size of the study population...
  5. Machens A, Hauptmann S, Dralle H. Modification of multiple endocrine neoplasia 2A phenotype by cell membrane proximity of RET mutations in exon 10. Endocr Relat Cancer. 2009;16:171-7 pubmed publisher
    ..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...
  6. Kahraman T, de Groot J, Rouwe C, Hofstra R, Links T, Sijmons R, et al. Acceptable age for prophylactic surgery in children with multiple endocrine neoplasia type 2a. Eur J Surg Oncol. 2003;29:331-5 pubmed
    ..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...
  7. Peczkowska M, Januszewicz A. Multiple endocrine neoplasia type 2. Fam Cancer. 2005;4:25-36 pubmed
    ..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...
  8. Dvorakova S, Dvorakova K, Malíková M, Skaba R, Vlcek P, Bendlova B. A novel Czech kindred with familial medullary thyroid carcinoma and Hirschsprung's disease. J Pediatr Surg. 2005;40:e1-6 pubmed
    ..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...
  9. Moore S, Zaahl M. Familial associations in medullary thyroid carcinoma with Hirschsprung disease: the role of the RET-C620 "Janus" genetic variation. J Pediatr Surg. 2010;45:393-6 pubmed publisher
    ..Specifically, HSCR-MEN2 cosegregation mostly relates to the cysteine-rich area at the RET-620 (the "Janus gene")...
  10. Frank Raue K, Rybicki L, Erlic Z, Schweizer H, Winter A, Milos I, et al. Risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germline RET mutations located in exon 10. Hum Mutat. 2011;32:51-8 pubmed publisher
    ..Our data provide rigorous bases for timing of premorbid diagnosis and personalized treatment/prophylactic procedure decisions depending on specific RET exon 10 codons affected...
  11. McIntyre E, Bond P, Douglas F, Lennard T, Peaston R, Perros P. Multiple endocrine neoplasia type 2A: an unusual clinical presentation and association with renal dysplasia. Cancer Genet Cytogenet. 2003;141:157-9 pubmed
    We 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...
  12. Erlic Z, Hoffmann M, Sullivan M, Franke G, Peczkowska M, Harsch I, et al. Pathogenicity of DNA variants and double mutations in multiple endocrine neoplasia type 2 and von Hippel-Lindau syndrome. J Clin Endocrinol Metab. 2010;95:308-13 pubmed publisher
    ..This observation of coincident DNA variants, both reported as pathogenic, in two known susceptibility genes prompted the question of their pathogenic relevance...
  13. Machens A, Dralle H. Familial prevalence and age of RET germline mutations: implications for screening. Clin Endocrinol (Oxf). 2008;69:81-7 pubmed
    ..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...
  14. Frank Raue K, Rondot S, Schulze E, Raue F. Change in the spectrum of RET mutations diagnosed between 1994 and 2006. Clin Lab. 2007;53:273-82 pubmed
    ..In our series 38.9% of mutations were level 1 mutations, 54.4% level 2, and 5.6% level 3 mutations...
  15. Marsh D, Theodosopoulos G, Martin Schulte K, Richardson A, Philips J, Röher H, et al. Genome-wide copy number imbalances identified in familial and sporadic medullary thyroid carcinoma. J Clin Endocrinol Metab. 2003;88:1866-72 pubmed
    ..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...
  16. Kjaer S, Kurokawa K, Perrinjaquet M, Abrescia C, Ibanez C. Self-association of the transmembrane domain of RET underlies oncogenic activation by MEN2A mutations. Oncogene. 2006;25:7086-95 pubmed
  17. Romei C, Cosci B, Renzini G, Bottici V, Molinaro E, Agate L, et al. 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). Clin Endocrinol (Oxf). 2011;74:241-7 pubmed publisher
    ..e. gene carriers) who are unaware of their condition...
  18. de Groot J, Plaza Menacho I, Schepers H, Drenth Diephuis L, Osinga J, Plukker J, et al. Cellular effects of imatinib on medullary thyroid cancer cells harboring multiple endocrine neoplasia Type 2A and 2B associated RET mutations. Surgery. 2006;139:806-14 pubmed
  19. Yip L, Cote G, Shapiro S, Ayers G, Herzog C, Sellin R, et al. Multiple endocrine neoplasia type 2: evaluation of the genotype-phenotype relationship. Arch Surg. 2003;138:409-16; discussion 416 pubmed
    ..Subtypes are defined by the presence or absence of pheochromocytomas, hyperparathyroidism, and characteristic clinical stigmas. We hypothesize that specific RET mutations correlate with the MEN 2 phenotype and aggressiveness of MTC...
  20. van Nederveen F, Korpershoek E, DeLeeuw R, Verhofstad A, Lenders J, Dinjens W, et al. Array-comparative genomic hybridization in sporadic benign pheochromocytomas. Endocr Relat Cancer. 2009;16:505-13 pubmed publisher
    ..In addition, genes on 21q and 22q might play a more important role in PCC pathogenesis than had been assumed thus far...
  21. Carling T. Multiple endocrine neoplasia syndrome: genetic basis for clinical management. Curr Opin Oncol. 2005;17:7-12 pubmed
    ..Improved understanding of the molecular and clinical genetics associated with these lesions will likely enhance the diagnosis and treatment of patients with these diseases...
  22. Saito T, Miura D, Taguchi M, Takeshita A, Miyakawa M, Takeuchi Y. Coincidence of multiple endocrine neoplasia type 2A with acromegaly. Am J Med Sci. 2010;340:329-31 pubmed publisher
    ..Although the simultaneous occurrence of both MEN2A and sporadic acromegaly may be accidental, there is evidence to suggest a genetic interaction between MEN2 and acromegaly...
  23. Szinnai G, Meier C, Komminoth P, Zumsteg U. Review of multiple endocrine neoplasia type 2A in children: therapeutic results of early thyroidectomy and prognostic value of codon analysis. Pediatrics. 2003;111:E132-9 pubmed
    ..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 ..
  24. Lesueur F, Cebrian A, Cranston A, Leyland J, Faid T, Clements M, et al. Germline homozygous mutations at codon 804 in the RET protooncogene in medullary thyroid carcinoma/multiple endocrine neoplasia type 2A patients. J Clin Endocrinol Metab. 2005;90:3454-7 pubmed
    ..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...
  25. Zhou Y, Zhao Y, Cui B, Gu L, Zhu S, Li J, et al. RET proto-oncogene mutations are restricted to codons 634 and 918 in mainland Chinese families with MEN2A and MEN2B. Clin Endocrinol (Oxf). 2007;67:570-6 pubmed
    ..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)...
  26. Hickey J, Myers S, Tian X, Zhu S, V Shaw J, Andrew S, et al. RET-mediated gene expression pattern is affected by isoform but not oncogenic mutation. Genes Chromosomes Cancer. 2009;48:429-40 pubmed publisher
    ..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...
  27. Butter A, Gagné J, Al Jazaeri A, Emran M, Deal C, St Vil D. Prophylactic thyroidectomy in pediatric carriers of multiple endocrine neoplasia type 2A or familial medullary thyroid carcinoma: mutation in C620 is associated with Hirschsprung's disease. J Pediatr Surg. 2007;42:203-6 pubmed
    ..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)...
  28. Skinner M, Moley J, Dilley W, Owzar K, DeBenedetti M, Wells S. Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med. 2005;353:1105-13 pubmed
    ..We sought to determine whether total thyroidectomy in asymptomatic young members of kindreds with MEN-2A who had a mutated allele of the RET proto-oncogene could prevent or cure medullary thyroid carcinoma...
  29. Puñales M, da Rocha A, Meotti C, Gross J, Maia A. Clinical and oncological features of children and young adults with multiple endocrine neoplasia type 2A. Thyroid. 2008;18:1261-8 pubmed publisher
    ..This study aimed to describe the clinical presentation, oncological features, and treatment outcome of children and young adults harboring RET mutations followed at our institution from 1997 to 2007...
  30. Cuccuru G, Lanzi C, Cassinelli G, Pratesi G, Tortoreto M, Petrangolini G, et al. Cellular effects and antitumor activity of RET inhibitor RPI-1 on MEN2A-associated medullary thyroid carcinoma. J Natl Cancer Inst. 2004;96:1006-14 pubmed
    ..Medullary thyroid carcinoma is a component of multiple endocrine neoplasia type 2 or MEN2 syndromes...
  31. Sherer D, Dalloul M, Salame G, Kalidas P, Zinn H, Abulafia O. Gestational diabetes leading to diagnosis and management of multiple endocrine neoplasia type 2a. Obstet Gynecol. 2010;115:455-7 pubmed publisher
    ..Secondary diabetes rarely has been reported in association with principal endocrinopathies complicating pregnancy...
  32. Raue F, Frank Raue K. Update multiple endocrine neoplasia type 2. Fam Cancer. 2010;9:449-57 pubmed publisher
    ..MEN 2 gives a unique model for early prevention and cure of cancer and for stratified roles of mutation-based diagnosis of carriers...
  33. Toledo R, Wagner S, Coutinho F, Lourenço D, Azevedo J, Longuini V, et al. High penetrance of pheochromocytoma associated with the novel C634Y/Y791F double germline mutation in the RET protooncogene. J Clin Endocrinol Metab. 2010;95:1318-27 pubmed publisher
    ..Previous studies have shown that double RET mutations may be associated with unusual multiple endocrine neoplasia type 2 (MEN 2) phenotypes...
  34. Castellone M, Verrienti A, Magendra Rao D, Sponziello M, Fabbro D, Muthu M, et al. A novel de novo germ-line V292M mutation in the extracellular region of RET in a patient with phaeochromocytoma and medullary thyroid carcinoma: functional characterization. Clin Endocrinol (Oxf). 2010;73:529-34 pubmed publisher
    ..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...
  35. Milos I, Frank Raue K, Wohllk N, Maia A, Pusiol E, Patocs A, et al. Age-related neoplastic risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germ line RET Cys634Trp (TGC>TGG) mutation. Endocr Relat Cancer. 2008;15:1035-41 pubmed publisher
    ..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...
  36. Wohllk N, Schweizer H, Erlic Z, Schmid K, Walz M, Raue F, et al. Multiple endocrine neoplasia type 2. Best Pract Res Clin Endocrinol Metab. 2010;24:371-87 pubmed publisher
    ..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...
  37. Vaclavikova E, Dvorakova S, Sykorova V, Bilek R, Dvorakova K, Vlcek P, et al. RET mutation Tyr791Phe: the genetic cause of different diseases derived from neural crest. Endocrine. 2009;36:419-24 pubmed publisher
    ..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...
  38. Mian C, Barollo S, Zambonin L, Pennelli G, Bernante P, Pelizzo M, et al. Characterization of the largest kindred with MEN2A due to a Cys609Ser RET mutation. Fam Cancer. 2009;8:379-82 pubmed publisher
    ..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...
  39. Akerstrom G, Stalberg P. Surgical management of MEN-1 and -2: state of the art. Surg Clin North Am. 2009;89:1047-68 pubmed publisher
    ..Prophylactic thyroidectomy based on DNA testing in the MEN-2 syndrome is considered one of the greater achievements in cancer treatment, because it may be performed before thyroid carcinoma development and provides cure for the patient...
  40. Zenaty D, Aigrain Y, Peuchmaur M, Philippe Chomette P, Baumann C, Cornelis F, et al. Medullary thyroid carcinoma identified within the first year of life in children with hereditary multiple endocrine neoplasia type 2A (codon 634) and 2B. Eur J Endocrinol. 2009;160:807-13 pubmed publisher
    ..Early prophylactic thyroidectomy in patients with multiple endocrine neoplasia (MEN) type 2 offers the best chance for a normal life expectancy...
  41. Cohen M, Moley J. Surgical treatment of medullary thyroid carcinoma. J Intern Med. 2003;253:616-26 pubmed
    ..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...
  42. Hubner R, Houlston R. Molecular advances in medullary thyroid cancer diagnostics. Clin Chim Acta. 2006;370:2-8 pubmed
    ..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...
  43. Moore S, Zaahl M. Multiple endocrine neoplasia syndromes, children, Hirschsprung's disease and RET. Pediatr Surg Int. 2008;24:521-30 pubmed publisher
    ..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...
  44. de Groot J, Links T, Plukker J, Lips C, Hofstra R. RET as a diagnostic and therapeutic target in sporadic and hereditary endocrine tumors. Endocr Rev. 2006;27:535-60 pubmed
    ..However, a clinically useful therapeutic option for treating patients with RET-associated cancer is still not available...
  45. Toledo S, dos Santos M, Toledo R, Lourenço D. Impact of RET proto-oncogene analysis on the clinical management of multiple endocrine neoplasia type 2. Clinics (Sao Paulo). 2006;61:59-70 pubmed
  46. Macher H, Martinez Broca M, Rubio Calvo A, Leon Garcia C, Conde Sánchez M, Costa A, et al. Non-invasive prenatal diagnosis of multiple endocrine neoplasia type 2A using COLD-PCR combined with HRM genotyping analysis from maternal serum. PLoS ONE. 2012;7:e51024 pubmed publisher
    The multiple endocrine neoplasia type 2A (MEN2A) is a monogenic disorder characterized by an autosomal dominant pattern of inheritance which is characterized by high risk of medullary thyroid carcinoma in all mutation carriers...
  47. Eisenhofer G, Huynh T, Pacak K, Brouwers F, Walther M, Linehan W, et al. Distinct gene expression profiles in norepinephrine- and epinephrine-producing hereditary and sporadic pheochromocytomas: activation of hypoxia-driven angiogenic pathways in von Hippel-Lindau syndrome. Endocr Relat Cancer. 2004;11:897-911 pubmed
  48. Rohmer V, Vidal Trecan G, Bourdelot A, Niccoli P, Murat A, Wemeau J, et al. 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 Endocrines. J Clin Endocrinol Metab. 2011;96:E509-18 pubmed publisher
    ..In hereditary medullary thyroid carcinoma (HMTC), prophylactic surgery is the only curative option, which should be properly defined both in time and extent...
  49. Machens A, Dralle H. Pheochromocytoma penetrance varies by RET mutation in MEN 2A. Surgery. 2008;143:696; author reply 697 pubmed publisher
  50. Schulte K, Machens A, Fugazzola L, McGregor A, Diaz Cano S, Izatt L, et al. The clinical spectrum of multiple endocrine neoplasia type 2a caused by the rare intracellular RET mutation S891A. J Clin Endocrinol Metab. 2010;95:E92-7 pubmed publisher
    ..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...
  51. Richards M. Thyroid cancer genetics: multiple endocrine neoplasia type 2, non-medullary familial thyroid cancer, and familial syndromes associated with thyroid cancer. Surg Oncol Clin N Am. 2009;18:39-52, viii pubmed publisher
    ..Thyroid cancer also is associated with a number of familial syndromes. This article focuses on the genetics and management of familial thyroid cancers and the syndromes associated with thyroid cancer...
  52. Mukherjee S, Zakalik D. RET codon 804 mutations in multiple endocrine neoplasia 2: genotype-phenotype correlations and implications in clinical management. Clin Genet. 2011;79:1-16 pubmed publisher
    ..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...
  53. Calva D, O Dorisio T, Sue O Dorisio M, Lal G, Sugg S, Weigel R, et al. When is prophylactic thyroidectomy indicated for patients with the RET codon 609 mutation?. Ann Surg Oncol. 2009;16:2237-44 pubmed publisher
    Mutations in the RET proto-oncogene cause multiple endocrine neoplasia type 2A (MEN2A), and prophylactic thyroidectomy has generally been recommended before the age of 5 years...