Horm Metab Res 2005; 37(6): 343-346
DOI: 10.1055/s-2005-870183
Editorial
© Georg Thieme Verlag KG Stuttgart · New York

Multiple Endocrine Neoplasias in the Era of Translational Medicine

C.  A.  Stratakis1 , S.  J.  Marx2
  • 1Section on Endocrinology & Genetics, Developmental Endocrinology Branch, National Institute of Child Health and Human Development (NICHD)
  • 2Metabolic Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD, USA
Further Information

Publication History

Publication Date:
07 July 2005 (online)

Abstract

Medicine is an ever changing art, continuously adjusting to the shifting principles of philosophy and constant discoveries of science; it was beautifully said by Hippocrates: ”… medicine does not do the same thing at this moment and the next…” Unabated dissemination of information is the only way that patients are assured that physicians will continue to practice medicine that reflects contemporary science. In the field of Multiple Endocrine Neoplasias (MENs), this is at least in part accomplished by biennially held International Workshops. The articles led by this editorial are the second and last installment of a collection of state-of-the-art presentations given in the course of the ninth such workshop that was held in Bethesda, MD, June 19-22, 2004. In addition to serving as an introduction to the articles that were written by some of the leaders in the field, the text of the editorial review that follows also supports the notion that MENs are poised to lead translational research in endocrinology: these disorders have benefited remarkably from the discoveries of the human genome project and are at a unique position to take advantage of new modalities in basic and clinical science

References

  • 1 Carney J A. Familial multiple endocrine neoplasia: the first 100 years.  Am J Surg Pathol. 2005;  29 254-274
  • 2 Marx S J, Stratakis C A. Multiple endocrine neoplasia - introduction.  J Intern Med. 2005;  257 2-5
  • 3 Bilezikian J P, Brandi M L, Rubin M, Silverberg S J. Primary hyperparathyroidism: New concepts in clinical, densitometric, and biochemical features.  J Intern Med. 2005;  257 6-17
  • 4 Bradley K J, Hobbs M R, Buley I D, Carpten J D, Cavaco B M, Fares J E, Laidler P, Manek S, Robbins C M, Salti I S, Thompson N W, Jackson C E, Thakker R V. Uterine tumours are a phenotypic manifestation of the hyperparathyroidism-jaw tumour (HPT-JT) syndrome.  J Intern Med. 2005;  257 18-26
  • 5 Carling T, Udelsman R. Parathyroid surgery in familial hyperparathyroid disorders.  J Intern Med. 2005;  257 27-37
  • 6 Tonelli F, Gratini G, Falchetti A, Nesi G, Brandi M L. Surgery for gastroenteropancreatic tumours in multiple endocrine neoplasia type 1: review and personal experience.  J Intern Med. 2005;  257 38-49
  • 7 Machens A, Ukkat J, Brauckhoff M, Gimm O, Dralle H. Advances in the management of hereditary medullary thyroid cancer.  J Intern Med. 2005;  257 50-59
  • 8 Pacak K, Ilias I, Adams K T, Eisenhofer G. Biochemical diagnosis, localization, and management of pheochromocytoma: focus on multiple endocrine neoplasia type 2 in relation to other hereditary syndromes and sporadic forms of the tumour.  J Intern Med. 2005;  257 60-68
  • 9 Lips C J, Höppener J W, Van Nesselrooij B P, Van der Luijt R B. Counselling in multiple endocrine neoplasia syndromes: from individual experience to general guidelines.  J Intern Med. 2005;  257 69-77
  • 10 Daly A F, Jaffrain-Rea M-L, Beckers A. Clinical and genetic features of familial pituitary adenomas.  Horm Metab Res. 2005;  37 347-354
  • 11 Hao W, Skarulis M C, Simonds W F, Weinstein L S, Agarwal S K, Mateo C, James-Newton L, Hobbs G R, Gibril F, Jensen R T, Marx S J. Multiple endocrine neoplasia type 1 variant with frequent prolactinoma and rare gastrinoma.  J Clin Endocrinol Metab. 2004;  89 3776-3784
  • 12 Kirschner L S, Sandrini F, Monbo J, Lin J P, Carney J A, Stratakis C A. Genetic heterogeneity and spectrum of mutations of the PRKAR1A gene in patients with the carney complex.  Hum Mol Genet. 2000;  9 3037-3046
  • 13 Soares B S, Frohman L A. Isolated familial somatotropinoma.  Pituitary. 2004;  7 95-101
  • 14 De Menis E, Prezant T R. Isolated familial somatotropinomas: clinical features and analysis of the MEN1 gene.  Pituitary. 2002;  5 11-15
  • 15 Jorge B H, Agarwal S K, Lando V S, Salvatori R, Barbero R R, Abelin N, Levine M A, Marx S J, Toledo S P. Study of the multiple endocrine neoplasia type 1, growth hormone-releasing hormone receptor, Gs alpha, and Gi2 alpha genes in isolated familial acromegaly.  J Clin Endocrinol Metab. 2001;  86 542-544
  • 16 Stratakis C A, Kirschner L S. Isolated familial somatotropinomas: does the disease map to 11q13 or to 2p16?.  J Clin Endocrinol Metab. 2000;  85 4920-4921
  • 17 Ezzat S, Asa S L. FGF receptor signaling at the crossroads of endocrine homeostasis and tumorigenesis.  Horm Metab Res. 2005;  37 355-360
  • 18 Ezzat S, Zheng L, Asa S L. Pituitary tumor-derived fibroblast growth factor receptor 4 isoform disrupts neural cell-adhesion molecule/N-cadherin signaling to diminish cell adhesiveness: a mechanism underlying pituitary neoplasia.  Mol Endocrinol. 2004;  18 2543-2552
  • 19 Ezzat S, Huang P, Dackiw A, Asa S L. Dual inhibition of RET and FGFR4 restrains medullary thyroid cancer cell growth.  Clin Cancer Res. 2005;  11 1336-1341
  • 20 St Bernard R, Zheng L, Liu W, Winer D, Asa S L, Ezzat S. Fibroblast growth factor receptors as molecular targets in thyroid carcinoma.  Endocrinology. 2005;  146 1145-1153
  • 21 Farrell W E. Epigenetic mechanisms of tumorigenesis.  Horm Metab Res. 2005;  37 361-368
  • 22 Farrell W E, Clayton R N. Epigenetic change in pituitary tumorigenesis.  Endocr Relat Cancer. 2003;  10 323-330
  • 23 Bahar A, Bicknell J E, Simpson D J, Clayton R N, Farrell W E. Loss of expression of the growth inhibitory gene GADD45gamma, in human pituitary adenomas, is associated with CpG island methylation.  Oncogene. 2004;  23 936-944
  • 24 Simpson D J, McNicol A M, Murray D C, Bahar A, Turner H E, Wass J A, Esiri M M, Clayton R N, Farrell W E. Molecular pathology shows p16 methylation in nonadenomatous pituitaries from patients with Cushing's disease.  Clin Cancer Res. 2004;  10 1780-1788
  • 25 Hendy G N, Kaji H, Sowa H, Lebrun J-J, Canaff L. Menin and the TGF-β superfamily member signaling via the Smad pathway in pituitary, parathyroid, and osetoblast.  Horm Metab Res. 2005;  37 375-379
  • 26 Agarwal S K, Kennedy P A, Scacheri P C, Novotny E A, Hickman A B, Cerrato A, Rice T S, Moore J B, Rao S, Ji Y, Mateo C, Libutti S K, Oliver B, Chandrasekharappa S C, Burns A L, Collins F S, Spiegel A M, Marx S J. Menin molecular interactions: insights into normal functions and tumorigenesis.  Horm Metab Res. 2005;  37 369-374
  • 27 Marx S J. Molecular genetics of multiple endocrine neoplasia types 1 and 2.  Nat Rev Cancer. 2005;  5 367-375
  • 28 Hughes C M, Rozenblatt-Rosen O, Milne T A, Copeland T D, Levine S S, Lee J C, Hayes D N, Shanmugam K S, Bhattacharjee A, Biondi C A, Kay G F, Hayward N K, Hess J L, Meyerson M. Menin associates with a trithorax family histone methyltransferase complex and with the hoxc8 locus.  Mol Cell. 2004;  13 587-597
  • 29 Wang P F, Tan M-H, Zhang C, Marsh D, Morreau H, Teh B T. HRPT2, a tumor suppressor gene for hyperparathyroidism-jaw tumor syndrome.  Horm Metab Res. 2005;  37 380-383
  • 30 Shattuck T M, Valimaki S, Obara T, Gaz R D, Clark O H, Shoback D, Wierman M E, Tojo K, Robbins C M, Carpten J D, Farnebo L O, Larsson C, Arnold A. Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma.  N Engl J Med. 2003;  349 1722-1729
  • 31 Howell V M, Haven C J, Kahnoski K, Khoo S K, Petillo D, Chen J, Fleuren G J, Robinson B G, Delbridge L W, Philips J, Nelson A E, Krause U, Hammje K, Dralle H, Hoang-Vu C, Gimm O, Marsh D J, Morreau H, Teh B T. HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours.  J Med Genet. 2003;  40 657-663
  • 32 Haven C J, Howell V M, Eilers P H, Dunne R, Takahashi M, van Puijenbroek M, Furge K, Kievit J, Tan M H, Fleuren G J, Robinson B G, Delbridge L W, Philips J, Nelson A E, Krause U, Dralle H, Hoang-Vu C, Gimm O, Morreau H, Marsh D J, Teh B T. Gene expression of parathyroid tumors: molecular subclassification and identification of the potential malignant phenotype.  Cancer Res. 2004;  64 7405-7411
  • 33 Bertherat J, Gimenez-Roqueplo A-P. New insights in the genetics of adrenocortical tumors, pheochromocytomas, and paragangliomas.  Horm Metab Res. 2005;  37 384-390
  • 34 Bertherat J, Groussin L, Sandrini F, Matyakhina L, Bei T, Stergiopoulos S, Papageorgiou T, Bourdeau I, Kirschner L S, Vincent-Dejean C, Perlemoine K, Gicquel C, Bertagna X, Stratakis C A. Molecular and functional analysis of PRKAR1A and its locus (17q22 - 24) in sporadic adrenocortical tumors: 17q losses, somatic mutations, and protein kinase A expression and activity.  Cancer Res. 2003;  63 5308-5319
  • 35 Neumann H P, Bausch B, McWhinney S R, Bender B U, Gimm O, Franke G, Schipper J, Klisch J, Altehoefer C, Zerres K, Januszewicz A, Eng C, Smith W M, Munk R, Manz T, Glaesker S, Apel T W, Treier M, Reineke M, Walz M K, Hoang-Vu C, Brauckhoff M, Klein-Franke A, Klose P, Schmidt H, Maier-Woelfle M, Peczkowska M, Szmigielski C, Eng C.. Freiburg-Warsaw-Columbus Pheochromocytoma Study Group . Germ-line mutations in nonsyndromic pheochromocytoma.  N Engl J Med. 2002;  346 1459-1466
  • 36 Neumann H P, Pawlu C, Peczkowska M, Bausch B, McWhinney S R, Muresan M, Buchta M, Franke G, Klisch J, Bley T A, Hoegerle S, Boedeker C C, Opocher G, Schipper J, Januszewicz A, Eng C.. European-American Paraganglioma Study Group . Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations.  JAMA 2004 Aug. 25;  292 943-951
  • 37 Carney J A, Stratakis C A. Familial paraganglioma and gastric stromal sarcoma: a new syndrome distinct from the Carney triad.  Am J Med Genet. 2002;  108 132-139
  • 38 Wolf A, Willenberg H S, Cupisti K, Schott M, Geddert H, Raffel A, Bornstein S R, Scherbaum W A, Knoefel W T. Adrenal pheochromocytoma with contralateral cortisol-producing adrenal adenoma: diagnostic and therapeutic management.  Horm Metab Res. 2005;  37 391-395
  • 39 Hanahan D, Weinberg R A. The hallmarks of cancer.  Cell. 2000;  100 57-70
  • 40 Khan J, Wei J S, Ringner M, Saal L H, Ladanyi M, Westermann F, Berthold F, Schwab M, Antonescu C R, Peterson C, Meltzer P S. Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks.  Nat Med. 2001;  7 673-679
  • 41 Carlomagno F, Santoro M. Identification of RET kinase inhibitors as potential new treatment for sporadic and inherited thyroid cancer.  J Chemother. 2004;  16 49-51

Dr. C. A. Stratakis

Section on Endocrinology & Genetics, DEB, NICHD, NIH, Building 10, CRC, Room I-1330 ·

10 Center Drive · MSC 1103 · Bethesda · Maryland 20892-1103

Phone: +1-301-4964686/4021998 ·

Fax: +1-301-4020574

Email: stratakc@mail.nih.gov