title: Hirschsprung's disease and medullary thyroid carcinoma: 15-year experience with molecular genetic screening of the RET proto-oncogene.
abstract: OBJECTIVE
  Inactivating germline mutations in the RET proto-oncogene are the major genetic cause of Hirschsprung's disease (HD). In some cases, HD can be associated with medullary thyroid carcinoma (MTC) that is commonly caused by activating RET mutations.
  
  
  METHODS
  The retrospective and prospective genetic analyses of 157 patients with HD operated on between December 1979 and June 2011 were carried out. DNA was isolated from peripheral leukocytes. HD patients and family members were tested for RET mutations by direct sequencing and single-strand conformation polymorphism methods.
  
  
  RESULTS
  RET mutations were detected in 16 patients (10%). Association with MTC was found in two families, other eight families had a mutation with potentially high risk of MTC development and four novel mutations were detected. Total colonic aganglionosis was noted to have a high mutation detection rate (40%). Three patients underwent total thyroidectomy (two had clinical manifestation of MTC, one C-cell hyperplasia).
  
  
  CONCLUSIONS
  Results show the benefit of systematic RET mutation screening in HD patients in order to identify the risk of MTC in the preclinical stage of the disease. All patients should be tested for RET mutations at least in exon 10, and now additionally in exon 11 and 13, as well.
authors: Department of Molecular Endocrinology, Institute of Endocrinology, Narodni trida 8, 11694, Prague 1, Czech Republic. evaclavikova@endo.cz
authors: Eliska
authors: E
authors: Vaclavikova
authors: Lucie
authors: L
authors: Kavalcova
authors: Richard
authors: R
authors: Skaba
authors: Sarka
authors: S
authors: Dvorakova
authors: Pavla
authors: P
authors: Macokova
authors: Blanka
authors: B
authors: Rouskova
authors: Bela
authors: B
authors: Bendlova
mesh_terms: D000293:Adolescent; D000328:Adult; D000369:Aged, 80 and over; D018278:Carcinoma, Neuroendocrine; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D005820:Genetic Testing / Q000379:methods*; D006627:Hirschsprung Disease / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011446:Prospective Studies; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D013964:Thyroid Neoplasms / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D013997:Time Factors
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret