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- W2004166021 abstract "A major gene causing Hirschsprung's disease was recently mapped in 10q11.2. Its physical localization was restricted to a 250-Kb interval containing the RET protooncogene (REarranged during Transfection). In 1994, point mutations affecting the RET proto-oncogene were identified in patients with Hirschsprung's disease. The authors present an immunohistochemical study on the expression and localization of the Ret protein (a receptor tyrosine kinase, which is the RET proto-oncogene product) in the intestinal plexuses of patients with Hirschsprung's disease. Ninety-two full-thickness intestinal wall pieces from 29 pediatric patients were studied (19 cases of classic Hirschsprung's disease, 5 of total colonic aganglionosis, and 5 controls). Ret protein immunohistochemical localization was obtained using c-Ret R5, anti-Ret K and anti-Ret C antibodies, respectively, against the extracellular domain, the tyrosine kinase domain, and the carboxy-terminal 20 amino acids of the Ret protein. A diffuse granular staining was present in the ganglia of normal colon, whereas the small ganglia of the hypoganglionic colon showed a reduced number of ganglion cells that were strongly stained with c-Ret R5 MoAb. A reduced synthesis of Ret protein was shown in the ganglionic and hypoganglionic segments of two cases of this series, the first with a complete deletion of the RET proto-oncogene and the second with a frameshift mutation and a stop codon in the extracellular domain. The activity of the receptor tyrosine kinases (RTKs) in intestinal ganglion cells was investigated using antiphosphotyrosine antibodies. A very low tyrosine kinase activity was shown in the small ganglia of the hypoganglionic segment. The results of this study suggest a primary role of this transmembrane receptor in the migration and differentiation of neural crest-derived neuroblasts that colonize the colon. The identification of the Ret protein ligand will better explain the role of this transmembrane receptor in the molecular and cellular mechanisms of Hirschsprung's disease." @default.
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- W2004166021 date "1995-03-01" @default.
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- W2004166021 title "Immunohistochemical localization of RET protein in Hirschsprung's disease" @default.
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- W2004166021 doi "https://doi.org/10.1016/0022-3468(95)90049-7" @default.
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