期刊论文详细信息
Italian Journal of Pediatrics
Multiple endocrine neoplasias type 2B and RET proto-oncogene
Sergio Bernasconi3  Carmine G Del Rossi2  Laura Lombardi2  Gian Paolo Tonini1  Lara Bricco4  Margherita Lerone4  Giuseppe Martucciello5 
[1] Traslational Oncopathology National Cancer Research Institute, Genova (16100), Italy;Department of Pediatric Surgery, Ospedale Maggiore, Via Antonio Gramsci 14, Parma (43010), Italy;Director Pediatric Department, University of Parma (43010), Italy;Laboratory of Molecular Genetic, Istituto G. Gaslini, Genova (16147), Italy;University of Genova, Associate Professor of Pediatric Surgery - DIPE, Via Gaslini, 5 Genova (16147), Italy
关键词: Hirschsprung's disease;    Neuroblastoma;    Thyroidectomy;    RET proto-oncogene;    Medullary Thyroid Carcinoma;    Multiple Endocrine Neoplasia;    MEN 2B;    Cancer;    Neural Crest Cells;    Neurocristopathies;   
Others  :  1146586
DOI  :  10.1186/1824-7288-38-9
 received in 2012-01-30, accepted in 2012-03-19,  发布年份 2012
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【 摘 要 】

Multiple Endocrine Neoplasia type 2B (MEN 2B) is an autosomal dominant complex oncologic neurocristopathy including medullary thyroid carcinoma, pheochromocytoma, gastrointestinal disorders, marphanoid face, and mucosal multiple ganglioneuromas. Medullary thyroid carcinoma is the major cause of mortality in MEN 2B syndrome, and it often appears during the first years of life. RET proto-oncogene germline activating mutations are causative for MEN 2B. The 95% of MEN 2B patients are associated with a point mutation in exon 16 (M918/T). A second point mutation at codon 883 has been found in 2%-3% of MEN 2B cases. RET proto-oncogene is also involved in different neoplastic and not neoplastic neurocristopathies. Other RET mutations cause MEN 2A syndrome, familial medullary thyroid carcinoma, or Hirschsprung's disease. RET gene expression is also involved in Neuroblastoma. The main diagnosis standards are the acetylcholinesterase study of rectal mucosa and the molecular analysis of RET. In our protocol the rectal biopsy is, therefore, the first approach. RET mutation detection offers the possibility to diagnose MEN 2B predisposition at a pre-clinical stage in familial cases, and to perform an early total prophylactic thyroidectomy. The surgical treatment of MEN 2B is total thyroidectomy with cervical limphadenectomy of the central compartment of the neck. When possible, this intervention should be performed with prophylactic aim before 1 year of age in patients with molecular genetic diagnosis. Recent advances into the mechanisms of RET proto-oncogene signaling and pathways of RET signal transduction in the development of MEN 2 and MTC will allow new treatment possibilities.

【 授权许可】

   
2012 Martucciello et al; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Sipple JH: "The association of pheochromocytoma with carcinoma of the thyroid gland". American Journal of Medicine 1961, 31:163-166.
  • [2]Ihara M, Yamashita T, Okamoto T, et al.: "A nationwide clinical survey of patients with multiple endocrine neoplasia type 2 and familial medullary carcinoma in Japan". Japanese Journal Clinical Oncology 1997, 27:128-134.
  • [3]Martucciello G, Ceccherini I, Lerone M, et al.: " Pathogenesis of Hirschsprung's disease". Journal of Pediatric Surgery 2000, 35:1017-1025.
  • [4]Romeo G, Ronchetto P, Lou Y, et al.: "Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirscsprung's disease". Nature 1994, 367:377-378.
  • [5]Martucciello G, Luinetti O, Romano P, Magrini U: "Molecular biology, basic research and diagnosis of Hirshsprung's disease". Pathologe 2007, 28(2):119-124.
  • [6]Martucciello G: "Hirschsprung's disease, one of the most difficult diagnoses in pediatric surgery: a review of the problems from clinical practice to the bench". European Journal of Pediatric Surgery 2008, 18(3):140-149.
  • [7]Seri M, Yin L, Barone V, et al.: "Detection of Ret mutations in higher among long segment than short segment Hirschsprung patient". Human Mutation 1997, 9:243-249.
  • [8]Romeo G, Ceccherini I, Celli J, et al.: "Association of multiple endocrine neoplasia type 2 and Hirschsprung disease". Journal of Internal Medicine 1998, 243:515-520.
  • [9]Molenaar JC, Brooks A, Meijers C: "Neurocristopathies. From basic science to clinical practice", Gaslini 1998, 30:105-110.
  • [10]Martucciello G: "Hirschsprung's disease as a neurochristopathy". Pediatric Surgery International 1997, 12:2-10.
  • [11]Bolande RP: "The neurocristopathies. a unifying concept of disease arising in neural crest maldevelopment", Human Pathology 1974, 5:409-429.
  • [12]Bronner-Fraser M: "Segregation of cell lineage in the neural crest". Current Opinion Genetic Development 1993, 3:641-647.
  • [13]Morre SW, Zaahl MG: "Multiple endocrine neoplasia syndromes. children, Hirschsprung'disease and RET", Pediatric Surgery International 2008, 24:521-520.
  • [14]Raue F, Franke-Raue K: "Update multiple endocrine neoplasia type 2". Familial Cancer 2010, 9:449-457.
  • [15]Shocket E, Teloh HA: "Aganglionic megacolon, phaeochromocytoma, megaloureter and neurofibromatosis". American Journal of Diseases of Children 94:185-191.
  • [16]Moore SW: "Neurocristopathies and particular associations with Hirscsprung's disease". "Hirschsprung's disease and allied disorders" Third edition. Edited by Springer. Holschneider, Puri Eds 2008, 18:243-266.
  • [17]Brandi ML, Gagel RF, Angeli A, et al.: "Guidelines for diagnosis and therapy of MEN type 1 and type 2". The Journal of Clinical Endocrinology and Metabolism 2001, 86:5658-5671.
  • [18]Engiz O, Ocal G, Siklar Z, et al.: "Early prophylactic thyroidectomy for Ret mutation-positive MEN 2B". Japan Pediatric Society 2007, 590-593.
  • [19]Camacho CP, Hoff AO, Linsdey SC, et al.: " Early diagnosis of Multiple Endocrine Neoplasia type 2B: a challenge for physicians". Arq Bras Endocrinol Metab 2008, 52/8:1393-1398.
  • [20]Morrison PJ, Nevin NC: "Multiple Endorine neoplasia type 2B (mucosal neuroma syndrome. Wagenmann-Froboese syndrome", Journal of Medical Genetics 1996, 33:779-782.
  • [21]Sallai A, Hosszù E, Gergics P, et al.: "Orolabial signs are important clues for diagnosis of the rare endocrine syndrome MEN 2B. presentation of two unrelated cases", European Journal of Pediatrics 2008, 167:441-446.
  • [22]Wray CJ, Rich TA, Waguespack SG, et al.: "Failure to recognize multiple endocrine neoplasia 2B: more common than we think?". Annals of Surgical Oncology 2007, 15(1):293-301.
  • [23]Lee NC, Norton JA: "Multiple endocrine neoplasia type 2B-genetic basis and clinical expression". Surgical Oncology 2000, 9:111-118.
  • [24]Lee MJ, Chung KH, Park JS, et al.: "Multiple endocrine neoplasia type 2B: early diagnosis by multiple mucosal neuroma and its DNA analysis". Annals of Dermatology vol 22 2010, 4:452-455.
  • [25]Brauckhoff M, Machens A, Hess S, et al.: "Premonitory symptoms preceding metastatic medullary thyroid cancer in MEN 2B: an exploratory analysis". Surgery 2008, 144:1044-1051.
  • [26]Skinner MA, de Benedetti MK, Moley JF, et al.: "Medullary Thyroid Carcinoma in Children With Multiple Endocrine Neoplasia Types 2A and 2B". Journal of Pediatric Surgery 1996, 31:177-182.
  • [27]Heshmati HM, Gharib H, van Heerden JA, et al.: "Advances and controversies in the diagnosis and management of Medullary Thyroid Carcinoma". American Journal of Medicine 1997, 103:60-69.
  • [28]Telenius-Berg M, Almqvist S, Berg B, et al.: "Screening for medullary carcinoma of the thyroid in families with Sipple's syndrome: evaluation of new stimulation tests". European Journal of Clinical Investigation 1997, 7:7-16.
  • [29]Karnovsky MJ, Roots L: "A direct-coloring thiocholine method for cholinesterase". Journal of Hisochemestry and Cytochemestry 1964, 12:219-221.
  • [30]Mukherjee S, Zakalik D: "RET codon 804 mutations in multiple endocrine neoplasia 2: genotype-phenotype correlations and implications in clinical management". Clinical Genetics 2011, 79:1-16.
  • [31]Russo A, Zanna I, Tubiolo C, et al.: "Hereditary common cancers: molecular and clinical genetics". Anticancer Research 2000, 20:4841-4851.
  • [32]O'Riordain DS, O'Brien T, Crotti TB, et al.: "Multiple endocrine neoplasia type 2B: more than an endocrine disorder". Surgery 1995, 118:936-942.
  • [33]Ponder J: "The phenotype associated with RET mutations in the multiple endocrine neoplasia type 2 syndrome". Cancer Research 1999, 59S:1736-1742.
  • [34]Hansford JR, Mulligan LM: "Multiple endocrine neoplasia type 2 and RET: from neoplasia to neurogenesis". Journal of Medical Genetics 2000, 37:817-27.
  • [35]Gimm O, Marsh DJ, Andrew SD, Frilling A, et al.: "Germline dinucleotide mutation in codon 883 of the RET proto-oncogene in multiple endocrine neoplasia type 2B without codon 918 mutation". The Journal of Clinical Endocrinology and Metabolism 1997, 82:3902-3904.
  • [36]Smith DP, Houghton C, Ponder BA: "Germiline mutation of RET codon 883 in two cases of de novo MEN 2B". Oncogene 1997, 15:1213-1217.
  • [37]Miyauchi A, Futami H, Hai N, et al.: "Two germline missense mutations at codons 804 and 806 of the RET proto- oncogene in the same allele in a patient with multiple endocrine neoplasia type 2B without codon 918 mutation". Japanese Journal of Cancer Research 1999, 90:1-5.
  • [38]Cranston AN, Carniti C, Oakhill K, et al.: "RET is constitutively activated by novel tandem mutations that alter the active site resulting in multiple endocrine neoplasia type 2B". Cancer Research 2006, 66:10179-10187.
  • [39]Menko FH, van der Luijt RB, de Valk IA, et al.: "Atypical MEN type 2B associated with two germline RET mutations on the same allele not involving codon 918". The Journal of Clinical Endocrinology and Metabolism 2002, 87:393-397.
  • [40]Hofstra RM, Wu Y, Stulp RP, et al.: "RET and GDNF gene scanning in Hirschsprung patients using two dual denaturing gel systems". Human Mutation 2000, 15:418-29.
  • [41]Garver KL, Law JC, Garver B: "Hirschsprung disease: a genetic study". Clinical Genetics 1985, 28(6):503-508.
  • [42]Badner JA, Sieber WK, Garver KL, et al.: "A genetic study of Hirschsprung disease". American Journal of Human Genetics 1990, 46:568-580.
  • [43]Martucciello G, Bicocchi MP, Dodero P, et al.: "Total colonic aganglionosis associated with interstitial deletion of the long arm of chromosome 10". Pediatric Surgery 1992, 7:308-310.
  • [44]Ceccherini I, Yin L, Pasini B, et al.: "Close linkage with RET protoncogene and deletion mutation in autosomal dominant Hirschsprung disease". Human Molecular Genetics 1993, 2, 11:1803-1808.
  • [45]Takahashi M, Burma Y, Iwamoto T, et al.: "Cloning and expression of the RET protoncogene encoding a tyrosine kinase with two potential transmembrane domains". Oncogene 1988, 3:571-578.
  • [46]Takahashi M, Burma Y, Hiai H: "Isolation of the RET protoncogene cDNA with an aminoterminal signal sequence". Oncogene 1989, 4:805-806.
  • [47]Ceccherini I, Bocciardi R, Yin L: "Exon structure and flanking intronic sequences of the human RET proto-oncogene". Biochemical and Biophysical Research Communication 1993, 196:1288-1295.
  • [48]Ceccherini I, Hofstra RM, Lou Y, et al.: " DNA polymorphisms and conditions for SSCP analysis of the 20 exons of the RET proto-oncogene". Oncogene 1994, 9:3025-3029.
  • [49]Meijers JH, van der Sanden MP, Tibboel D, et al.: "Colonization characteristics of enteric neural crest cells: embryological aspects of Hirschsprung's disease". Journal of Pediatric Surgery 1992, 27(7):811-814.
  • [50]Chakravarti A, Lyonnet S: "Hirschsprung disease". In The Metabolic and Molecular Bases of Inherited Disease. 8th edition. Edited by Scriver Cr, Beaudet Al, Valle D, Sly W. McGrw-Hill, New York; 2000.
  • [51]Ito S, Iwashita T, Asai N, et al.: "Biological properties of Ret with cysteine mutations correlate with multiple endocrine neoplasia type 2A, familial medullary thyroid carcinoma and Hirschsprung's disease phenotype". Cancer Research 1997, 57(14):2870-2872.
  • [52]Borrego S, Saez ME, Ruiz A, et al.: "Specific polymorphism in the RET proto-oncogene are over-represented in patients with Hirschsprung disease and may represent loci modifying phenotypic expression". Journal of Medical Genetics 1999, 36:771-774.
  • [53]Fitze G, Schreiber M, Kuhlisch E, et al.: "Association of RET protoncogene codon 45 polymorphism with Hirschsprung disease". American Journal of Human Genetics 1999, 65:1469-1473.
  • [54]Bolk S, Pelet A, Hofstra RM, et al.: "A humans model for multigenic inheritance: phenotypic expression in Hirschsprung disease requires both the Ret gene and a new 9q31 locus". Proceedings of the National Academy of Science of The United States of America 2000, 97(1):268-273.
  • [55]Gabriel SB, Salomon R, Pelet A, et al.: " Segregation at three loci explains familial and population risk in Hirschsprung disease". Nature Genetics 2002, 31:89-93.
  • [56]Amiel J, Lyonnet S: "Hirschsprung disease. associated syndromes, and genetics: a review", Journal of Medical Genetics 2001, 38:729-739.
  • [57]Carrasquillo MM, McCallion AS, Puffenberg EG, et al.: "Genome-wide association study and mouse model identify interaction between RET and EDNRB pathways in Hirschsprung disease". Nature Genetics 2002, 32:237-244.
  • [58]Ponder LM, Ponder BA: "Genetic basis of endocrine disease multiple endocrine neoplasia type 2". The Journal of Clinical Endocrinology and Metabolism 1995, 80:1989-1995.
  • [59]Borrego S, Ruiz A, Saez ME, et al.: "RET genotypes comprising specific haplotypes of polimorphic variants predispose to isolated Hirschsprung disease". Journal of Medical Genetics 2000, 37:572-578.
  • [60]Griseri P, Sancandi M, Patrone G, et al.: " A single-nucleotide polymorphic variant of the RET proto-oncogene is underrepresented in sporadic Hirschsprung disease". European Journal of Human Genetics 2000, 8:721-724.
  • [61]Fitze G, Cramer J, Ziegler A, et al.: "Association between c135G/A genotype and RET protoncogene germiline mutations and phenotype of Hirschsprung's disease". Lancet 2002, 6:1200-1205.
  • [62]Griseri P, Pesce B, Patrone G, et al.: "A rare haplotype of the RET proto-oncogene is a risk-modifying allele in Hirschsprung disease". American Journal of Human Genetics 2002, 71:969-974.
  • [63]Ceccherini I, Sancandi M, Griseri P, et al.: "Single nucleotide polymorphic allele in the 5' region of the RET proto-oncogene define a risk haplotype in Hirschsprung's disease". Journal of Medical Genetics 2003, 49:714-718.
  • [64]Hofstra RM, Chang NC, Hansen C, et al.: "No mutations found by RET mutation scanning in sporadic and hereditary neuroblastoma". Human Genetics 1996, 97:362-364.
  • [65]Peaston AE, Camacho ML, Norris MD, et al.: "Absence of MEN2A- or 2B-type RET mutations in primary neuroblastoma tumour tissue". Molecular and Cellular Probes 1998, 12:239-242.
  • [66]Leone A, Seeger RC, Hong CM, et al.: "Evidence for nm23 RNA overexpression, DNA amplification and mutation in aggressive childhood neuroblastomas". Oncogene 1993, 8:855-865.
  • [67]Maris J, Tonini GP: "Genetics of familial neuroblastoma". In Neuroblastoma. Edited by Brodeur GM, Sawada T, Tsuschida Y, Vote PA. Elsevier, Amsterdam; 2000:125-135.
  • [68]D'Alessio A, De Vita G, Calì G, et al.: "Expression of the RET oncogene induces differentiation of SK-N-BE neuroblastoma cells". Cell Growth and Differentiation 1995, 6(11):1387-1394.
  • [69]Esposito CL, D'Alessio A, de Franciscis V, et al.: "A cross-talk between TrkB and Ret tyrosine kinases receptors mediates neuroblastoma cells differentiation". Public Library of Science One 2008, 20;3(2):e1643.
  • [70]Bachetti T, Borghini S, Ravazzolo R, et al.: "An in vitro approach to test the possible role of candidate factors in the transcriptional regulation of the RET proto-oncogene". Gene Expression Pattern 2005, 12(3):137-149.
  • [71]Kurotsuchi A, Murakumo Y, Jijiwa M, et al.: "Analysis of DOK-6 function indownstream signaling of RET in human neuroblastoma cells". Cancer Science 2010, 101(5):1147-1155.
  • [72]Matthay KK, Tan JC, Villablanca JG, et al.: "Phase I dose escalation of iodine-131-metaiodobenzylguanidine with myeloablative chemotherapy and autologous stem-cell transplantation in refractory neuroblastoma: a new approaches to Neuroblastoma". Therapy Consortium Study, Journal of Clinical Oncology 20 2006, 24(3):500-506.
  • [73]Angrisano T, Sacchetti S, Natale F, et al.: "Chromatin and DNA methylation dynamics during retinoic acid-induced RET gene transcriptional activation in neuroblastoma cells". Nucleic Acids Research 2011, 39(6):1993-2006.
  • [74]Dralle H, Scheumann GFW, Kotzerke J, et al.: "Surgical management of MEN 2. Recent Results" Cancer Research 1992, 125:167-195.
  • [75]Martucciello G, Caffarena PE, Lerone M, et al.: "Neuronal Intestinal Displasia: clinical Experience in Italian Patients". European Journal of Pediatric Surgery 1994, 4:287-292.
  • [76]Iler MA, King RD, Ginn-Pease ME, et al.: "Multiple endocrine neoplasia type 2A: a 25-year review". Journal of Pediatric Surgery 1999, 34:92-97.
  • [77]Van Heurn LW, Svhaap C, Sie G, et al.: "Predictive DNA testing for multiple endocrine neoplasia 2: a therapeutic challenge of prophylactic thyroidectomy in very young children". Journal of Pediatric Surgery 1999, 34:568-571.
  • [78]Wells SA, Chi DD, Toshima K, et al.: "Predictive DNA testing and prophylactic thyroidectomy in patients at risk for Multiple Endocrine Neoplasia type 2A". Annals of Surgery 1994, 220:237-250.
  • [79]Decker RA, Peacock ML, Borst MJ, Sweet J: "Progress in genetic screening of multiple endocrine neoplasia type 2A: Is calcitonin testing obsolete?". Surgery 1995, 118:257-264.
  • [80]Decker RA, Peacock ML, Watson P: " Hirschsprung disease in MEN2A: increased spectrum of RET exon 10 genotypes and strong genotype-phenotype correlation". Human Molecular Genetics 1998, 7:129-134.
  • [81]Dralle H, Scheumann GFW, Kotzerke J, et al.: "Surgical management of MEN 2". Recent Results Cancer Research 1992, 125:167-195.
  • [82]Borst MJ, Van Camp JM, Peacock ML, et al.: "Mutational anlysis of multiple endocrine neoplasia type 2A associated with Hirschsprung's disease". Surgery 1995, 117:386-391.
  • [83]Eng C, Clayton D, Schuffenecker I, et al.: "The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2". Journal of American Medical Association 1996, 276:1575-1579.
  • [84]Torre M, Martucciello G, Ceccherini I, et al.: "Diagnostic and therapeutic approach to multiple endocrine neoplasia type 2B in pediatric patients". Pediatric Surgery International 2002, 18:378-383.
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