Información del artículo
Aproximadamente, el 5-10% de los tumores neuroendocrinos gastroenteropancreáticos tienen un componente hereditario conocido. Existen diferentes síndromes familiares tumorales de origen genético como el síndrome de neoplasia endocrina múltiple tipo 1 (MEN 1), la enfermedad de Von Hippel-Lindau (VHL), la neurofibromatosis tipo 1 (NF 1) y la esclerosis tuberosa (ET).
En este artículo se revisan las principales características clínicas y genéticas de estos síndromes: los genes involucrados y las mutaciones específicas, la prevalencia de la enfermedad y su penetrancia, los tejidos neuroendocrinos afectados, y las características morfológicas de los tumores neuroendocrinos GEP en el seno de cada uno de los diferentes síndromes genéticos.
Palabras clave:
Tumores neuroendocrinos
Neoplasia endocrina múltiple tipo 1
Menina
Enfermedad Von Hippel-Lindau
Factor inductor de hipoxia tipo 1
Neurofibromatosis
Esclerosis tuberosa
vía mTOR
Aproximately 5-10% of neuroendocrine tumours (NETs) of the gastroenteropancreatic system (GEP) have an hereditary background. The known hereditary syndromes include: multiple endocrine neoplasia type 1 (MEN 1), von Hippel Lindau disease (VHL), neurofibromatosis type 1 (NF 1) and tuberous sclerosis complex (TSC). This review discusses for each of these syndromes the: genes involved and specifics types of mutations, disease prevalence, affected neuroendocrine tissues and related clinical syndromes, and special morphological features of NETs on each of these syndromes.
Key words:
Neuroendocrine tumours
Multiple endocrine neoplasia type 1
Menin
Von Hippel-Lindau disease
Hipoxia-inducible transcription factor-1
Neurofibromatosis
Tuberous sclerosis disease
signal mTOR
El Texto completo está disponible en PDF
Bibliografía
[1.]
N. Alexakis, S. Connor, P. Ghaneh, M. Lombard, H.L. Smart, J. Evans, et al.
Hereditary pancreatic endocrine tumours.
Pancreatology, 4 (2004), pp. 417-433
[2.]
M. Anlauf, N. Garbrecht, J. Bauersfeld, A. Schmidt, T. Henopp, P. Komminoth, et al.
Hereditary neuroendocrine tumors of the gastroenteropancreatic system.
Virchows Arch, 451 (2007),
[3.]
Thakker RV. Genetics of non gastro-entero-pancreatic (GET) neuroendocrine tumors (NETs). a century of advances in neuroendocrine tumor biology and treatment. 2008. p. 192-9.
[4.]
M.L. Brandi, R.F. Gagel, A. Angeli, J.P. Bilerikian, P. Beck-Peccor, C. Bordin, et al.
Guidelines for diagnosis and therapy of MEN type 1 and type 2.
J Clin Endocrinol Metab, 86 (2001), pp. 5658
[5.]
D. Trump, B. Farren, C. Wooding, G.M. Besser, K.D. Buchanan, C.R. Edwards, et al.
Clinical studies of multiple endocrine neoplasia type 1 (MEN 1).
QJM, 89 (1996), pp. 653
[6.]
S.J. Marx, W.F. Simonds.
Hereditary hormone excess:genes, molecular pathways, and syndromes.
Endocr Rev, 26 (2005), pp. 615-661
[7.]
A. Calender, C.D. Morrison, P. Komminoth, J.Y. Scoazec, K.M. Sweet, B.T. The.
Multiple endocrine neoplasia type 1.
Pathology and genetics:tumors of endocrine organs. WHO classification of tumors, IARC, (2004),
[8.]
S.C. Chandrasekharappa, B. Tech.
Clinical and molecular aspects of multiple endocrine neoplasia type 1. Genetic disorders of endocrine neoplasia.
Karger, (2001),
[9.]
C. Heppner, M.B. Kester, S.K. Agarwal, L.V. Debelenko, M.R. Emmert-Buck, S.C. Guru, et al.
Somatic mutation of the MEN1 gene in parathyroid tumours.
Nat Genet, 16 (1997), pp. 375
[10.]
F. Farnebo, B.T. Teh, S. Kytölä, A. Svensson, C. Phelan, K. Sandelin, et al.
Alterations of the MEN1 gene in sporadic parathyroid tumors.
J Clin Endocrinol Metab, 83 (1998), pp. 2627
[11.]
M. Anlauf, N. Garbrecht, T. Henopp, A. Schmitt, R. Schlenger, A. Raffel, et al.
Sporadic versus hereditary gastrinomas of the duodenum and pancreas:distinct clinico-pathological and epidemiological features.
World J Gastroenterol, 12 (2006), pp. 5440-5446
[12.]
F. Gibril, M. Schumann, A. Pace, R.T. Jensen.
Multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome: a prospective study of 107 cases and comparison with 1009 cases from the literature.
Medicine (Baltimore), 83 (2004), pp. 43
[13.]
Anlauf M, Schlenger R, Perren A, Bauersfeld J, Koch CA, Gimm O, et al. Sporadic versus hereditary gastrinomas of the duodenum and pancreas:distinct clinic-pathological and epidemiological features. World J Gastroenterol. 12:5440-6.
[14.]
Bordi C, D’Adda T, Azzoni C, Ferraro G. Pathogenesis of ECL cell tumors in humans. Yale J Biol Med. 71:273-84.
[15.]
T.N. Darling, M.C. Skarulis, S.M. Steinberg, S.J. Marx, A.M. Spiegel, M. Turner.
Multiple facial angiofibromas and collagenomas in patients with multiple endocrine neoplasia type 1.
Arch Dermatol, 133 (1997), pp. 853
[16.]
R.R. Lonser, G.M. Glenn, M. Walther, E.Y. Chew, S.K. Libutti, W.H. Linehan, et al.
Von Hippel-Lindau disease.
Lancet, 361 (2003), pp. 2059
[17.]
Maher ER, Nathason K, Komminoth P, Neumann HPH, Plate KH, Bohling T. Von Hippel Lindau síndrome (VHL). Pathology and genetics: tumours of endocrine organs. WHO classification of tumors. Lyon: IARC; p. 230-7.
[18.]
W.Y. Kim, W.G. Kaelin.
Role of VHL gene mutation in human cancer.
J Clin Oncol, 22 (2004), pp. 4991
[19.]
R.E. Barry, W. Krek.
The von Hippel-Lindau tumour suppressor: a multi-faceted inhibitor of tumourigenesis.
Trends Mol Med, 10 (2004), pp. 466
[20.]
N. de Paulsen, A. Brychzy, M.C. Fournier, R.D. Klausner, J.R. Gnarra, A. Pause, et al.
Role of transforming growth factor-alpha in von Hippel—Lindau (VHL)(-/-) clear cell renal carcinoma cell proliferation:a possible mechanism coupling VHL tumor suppressor inactivation and tumorigenesis.
Proc Natl Acad Sci U S A, 98 (2001), pp. 1387
[21.]
Woodward ER, Maher ER. Von Hippel Lindau disease and endocrine tumour susceptibility. Endocr Related Cancer. 13:415-25.
[22.]
Libutti SK, Choyke PL, Alexander HR, Glenn G, Bartlett DL, Zbar B, et al. Clinical and genetic analysis of patients with pancreatic neuroendocrine tumors associated with von Hippel Lindau disease. Surgery. 128;1022-7.
[23.]
I.A. Lubensky, S. Pack, D. Ault, A.O. Vortmeyer, S.K. Libutti, P.L. Choyke, et al.
Multiple neuroendocrine tumors of the pancreas in von Hippel-Lindau disease patients: histopathological and molecular genetic analysis.
Am J Pathol, 153 (1998), pp. 223-231
[24.]
J.R. Yates.
Tuberous sclerosis.
Eur J Hum Genet, 14 (2006), pp. 415-425
[25.]
T.L. Plank, R.S. Yeung, E.P. Henske.
Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles.
Cancer Res, 58 (1998), pp. 4766-4770
[26.]
M. Van Slegtenhorst, M. Nellist, B. Nagelkerken, J. Cheadle, R. Snell, O.A. van den, et al.
Interaction betwewn hamartin and tuberin, the TSC1 and TSC2 gene products.
Hum Mol Genet, 7 (1998), pp. 1053-1057
[27.]
S.L. Dabora, S. Jozwiak, D.N. Franz, P.S. Roberts, A. Nieto, J. Chung, et al.
Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs.
Am J Hum Genet, 68 (2001), pp. 64-80
[28.]
O. Sancak, M. Nellist, M. Goedbloed, P. Elfferich, C. Wouters, A. Maat-kievit, et al.
Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting:genotype-phenotype correlations and comparison of diagnostic DNA techniques in tuberous sclerosis complex.
Eur J Hum Genet, 13 (2005), pp. 731-741
[29.]
T. Rosser, A. Panigraphy, W. McClintock.
The diverse clinical manifestations of tuberous sclerosis complex: a review.
Semin Pediatr Neurol, 13 (2006), pp. 27-36
[30.]
E.S. Roach, F.J. DiMario, R.S. Kandt, H. Northrup.
Tuberous Sclerosis Consensus Conference: recommendations for diagnostic evaluation. National Sclerosis Association.
J Child Neurol, 14 (1999), pp. 401-407
[31.]
L.F. Starker.
Carling molecular genetics of gastroenteropancreatic neuroendocrine tumors.
Curr Opin Oncol, 1 (2009), pp. 29-33
[32.]
D.H. Ledbetter, D.C. Rich, P. O’Conell, M. Leppert, J.C. Carey.
Precise localization of NF1 to 17q11.2 by balanced translocation.
Am J Hum Genet, 44 (1989), pp. 20-24
[33.]
D. Viskochil, A.M. Buchberg, G. Xu, R.M. Cawthon, J. Stevens, R.K. Wolff, et al.
Deletions and translocation interrupt a cloned gene at the neurofibromatosis type 1 locus.
Cell, 62 (1990), pp. 187-192
[34.]
S.S. Han, D.N. Cooper, M.N. Upadhyaya.
Evaluation of denaturing high performance liquid chromatography (DHPLC) for the mutational analysis of the neurofibromatosis type 1 (NF 1) gene.
Hum Genet, 109 (2001), pp. 487-497
[35.]
K. DeBella, J. Szudek, J.M. Friedman.
Use of the National Institutes of Health Crietria for Diagnosis of Neurofibromatosis 1 in children.
Pediatrics, 105 (2000), pp. 608-614
[36.]
Evans DGR, Komminoth P, Scheithauer BW, Peltonen J. Neurofibromatosis type 1. Pathology and genetics:tumours of endocrine organs. WHO classification of tumors. Lyon: IARC; p. 243-8.
[37.]
S. Tanaka, S. Yamasaki, H. Matsushita, Y. Ozawa, A. Kurosaki, K. Takeuchi, et al.
Duodenal Somatostatinoma: a case report and review of 31 cases with special reference to the relationship between tumor Ne and metastasis.
Pathol Int, 50 (2000), pp. 146-152
[38.]
A. Harry, M.F. Heymann, J. Bodic, J. Visset, J. Le Borgne, J.C. Leneel, et al.
Duodenal somatostatinoma. Anatomic Clinical Study of 12 operated cases.
Am Chir, 126 (2001), pp. 221-226
Copyright © 2009. Sociedad Española de Endocrinología y Nutrición
