We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Hirschsprung's disease and medullary thyroid carcinoma: 15-year experience with molecular genetic screening of the RET proto-oncogene.
- Authors
Vaclavikova, Eliska; Kavalcova, Lucie; Skaba, Richard; Dvorakova, Sarka; Macokova, Pavla; Rouskova, Blanka; Bendlova, Bela
- Abstract
Purpose: 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). Conclusion: 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.
- Subjects
HIRSCHSPRUNG'S disease; THYROID cancer; MOLECULAR genetics; GENETIC testing; PROTO-oncogenes; GENETIC mutation; GERM cells
- Publication
Pediatric Surgery International, 2012, Vol 28, Issue 2, p123
- ISSN
0179-0358
- Publication type
Article
- DOI
10.1007/s00383-011-2993-2