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RET Tyrosine Kinase Receptor

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Synonyms

CDHF12; CDHR16; HSCR1; MTC1; MEN2; PTC

Historical Background

RET (REarranged during Transfection) proto-oncogene, which locates on chromosome 10q11.2, encodes for a tyrosine kinase receptor that binds ligands of the GDNF (Glial-Derived Neurotrophic Factor) family (Maniè et al. 2001). It was first isolated in 1985 by Takahashi and coworkers (Takahashi et al. 1985) and later found rearranged in human thyroid papillary carcinoma (PTC) as a chimeric gene generated by fusion of RET tyrosine kinase with 5′ terminal region of a new gene called CCDC6, located on the same chromosome 10 (Grieco et al. 1990). RET is physiologically involved in the development of the central and peripheral nervous system, kidney, male germ cells, and thyroid calcitonin-secreting parafollicular C cells. In humans, loss-of-function mutations of RET cause congenital aganglionosis of the colon and impaired enteric nervous system formation, known as Hirschsprung’s disease, whereas RET gain-of-function...

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References

  • Ballerini P, Struski S, Cresson C, Prade N, Toujani S, Deswarte C, Dobbelstein S, Petit A, Lapillonne H, Gautier EF, Demur C, Lippert E, Pages P, Mansat-De Mas V, Donadieu J, Huguet F, Dastugue N, Broccardo C, Perot C, Delabesse E. RET fusion genes are associated with chronic myelomonocytic leukemia and enhance monocytic differentiation. Leukemia. 2012;26:2384–9.

    Article  PubMed  CAS  Google Scholar 

  • Castellone MD, Santoro M. Dysregulated RET signaling in thyroid cancer. Endocrinol Metab Clin N Am. 2008;37:363–74.

    Article  CAS  Google Scholar 

  • Flavin R, Jackl G, Finn S, Smyth P, Ring M, O’Regan E, Cahill S, Unger K, Denning K, Jinghuan L, Aherne S, Tallini G, Gaffney E, O’Leary JJ, Zitzelsberger H, Sheils O. RET/PTC rearrangement occurring in primary peritoneal carcinoma. Int J Surg Pathol. 2009;17:187–97.

    Article  PubMed  CAS  Google Scholar 

  • Gattelli A, Nalvarte I, Boulay A, Roloff TC, Schreiber M, Carragher N, Macleod KK, Schlederer M, Lienhard S, Kenner L, Torres-Arzayus MI, Hynes NE. Ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells. EMBO Mol Med. 2013;5:1335–50.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Grieco M, Santoro M, Berlingieri MT, Melillo RM, Donghi R, Bongarzone I, Pierotti MA, Della Porta G, Fusco A, Vecchio G. PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas. Cell. 1990;60:557–63.

    Article  PubMed  CAS  Google Scholar 

  • Guerra A, Di Crescenzo V, Garzi A, Cinelli M, Carlomagno C, Tonacchera M, Zeppa P, Vitale M. Genetic mutations in the treatment of anaplastic thyroid cancer: a systematic review. BMC Surg. 2013;13:S44.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kawamoto Y, Takeda K, Okuno Y, Yamakawa Y, Ito Y, Taguchi R, Kato M, Suzuki H, Takahashi M, Nakashima I. Identification of RET autophosphorylation sites by mass spectrometry. J Biol Chem. 2004;279:14213–24.

    Article  PubMed  CAS  Google Scholar 

  • Kohno T, Ichikawa H, Totoki Y, Yasuda K, Hiramoto M, Nammo T, Sakamoto H, Tsuta K, Furuta K, Shimada Y, Iwakawa R, Ogiwara H, Oike T, Enari M, Schetter AJ, Okayama H, Haugen A, Skaug V, Chiku S, Yamanaka I, Arai Y, Watanabe S, Sekine I, Ogawa S, Harris CC, Tsuda H, Yoshida T, Yokota J, Shibata T. KIF5B-RET fusions in lung adenocarcinoma. Nat Med. 2012;18:375–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kondo T, Ezzat S, Asa SL. Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer. 2006;6:292–306.

    Article  CAS  PubMed  Google Scholar 

  • Maniè S, Santoro M, Fusco A, Billaud M. The RET receptor: function in development and dysfunction in congenital malformation. Trends Genet. 2001;17:580–9.

    Article  PubMed  Google Scholar 

  • Nikiforov YE. RET/PTC rearrangement in thyroid tumors. Endocr Pathol. 2002;13:3–16.

    Article  PubMed  CAS  Google Scholar 

  • Santoro M, Melillo RM, Carlomagno F, Fusco A, Vecchio G. Molecular mechanisms of RET activation in human cancer. Ann N Y Acad Sci. 2002;963:116–21.

    Article  PubMed  CAS  Google Scholar 

  • Santoro M, Carlomagno F, Melillo RM, Fusco A. Dysfunction of the RET receptor in human cancer. Cell Mol Life Sci. 2004;61:2954–64.

    Article  PubMed  CAS  Google Scholar 

  • Santoro M, Carlomagno F. Drug insight: small-molecule inhibitors of protein kinases in the treatment of thyroid cancer. Nat Clin Pract Endocrinol Metab. 2006;2:42–52.

    Article  PubMed  CAS  Google Scholar 

  • Schlumberger M, Sherman SI. Clinical trials for progressive differentiated thyroid cancer: patient selection, study design, and recent advances. Thyroid. 2009;19:1393–400.

    Article  PubMed  Google Scholar 

  • Takahashi M, Ritz J, Cooper GM. Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell. 1985;42:581–8.

    Article  PubMed  CAS  Google Scholar 

  • Thomas GA, Bunnell H, Cook HA, Williams ED, Nerovnya A, et al. High prevalence of RET/PTC rearrangements in Ukrainian and Belarussian post-Chernobyl thyroid papillary carcinomas: a strong correlation between RET/PTC3 and the solid-follicular variant. J Clin Endocrinol Metab. 1999;84:4232–8.

    PubMed  CAS  Google Scholar 

  • Wells Jr SA, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, Baudin E, Elisei R, Jarzab B, Vasselli JR, Read J, Langmuir P, Ryan AJ, Schlumberger MJ. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012;30:134–41.

    Article  PubMed  CAS  Google Scholar 

  • Wiesner T, He J, Yelensky R, Esteve-Puig R, Botton T, Yeh I, Lipson D, Otto G, Brennan K, Murali R, Garrido M, Miller VA, Ross JS, Berger MF, Sparatta A, Palmedo G, Cerroni L, Busam KJ, Kutzner H, Cronin MT, Stephens PJ, Bastian BC. Kinase fusions are frequent in Spitz tumours and spitzoid melanomas. Nat Commun. 2014;5:3116.

    Article  PubMed  CAS  Google Scholar 

  • Williams D. Twenty years’ experience with post-Chernobyl thyroid cancer. Best Pract Res Clin Endocrinol Metab. 2008;22:1061–73.

    Article  PubMed  Google Scholar 

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Correspondence to Maria Domenica Castellone MD, PhD .

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Castellone, M.D., Laukkanen, M.O. (2018). RET Tyrosine Kinase Receptor. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101648

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