Clinical presentations and RET protooncogene mutations in seven multiple endocrine neoplasia type 2 kindreds Journal Article


Authors: Blank, R. D.; Sklar, C. A.; Dimich, A. B.; LaQuaglia, M. P.; Brennan, M. F.
Article Title: Clinical presentations and RET protooncogene mutations in seven multiple endocrine neoplasia type 2 kindreds
Abstract: BACKGROUND. Multiple endocrine neoplasia type 2 (MEN 2) is a group of related autosomal dominant cancer syndromes caused by mutations in the RET protooncogene. A subset of familial Hirschsprung's disease, aganglionic megacolon, is also caused by mutations in this gene. METHODS. The authors performed mutation analysis of exons 10, 11, 13, and 16 of the RET gene in six established MEN 2 kindreds and in six patients with apparent sporadic disease, in order to correlate their genotypes and phenotypes. RESULTS. One of these kindreds carried both Hirschsprung/s disease and MEN 2A in conjunction with a cysteine-to-arginine substitution of codon 620 of the RET gene. One patient with apparently sporadic disease was found to have a germline M918T mutation. Patients with confirmed familial disease all carried pathologic germline mutations of RET. CONCLUSIONS. Several lines of evidence support a gain of function mechanism for tumorigenesis in the MEN 2 syndromes but loss of function mechanism for aganglionosis in Hischsprung's disease. The authors propose that a multihit mechanism can reconcile the apparent paradox of a single mutation that gives rise to both gain and loss of function disorder in a single patient.
Keywords: adult; child; clinical article; middle aged; gene mutation; mutation; phenotype; disease association; proto oncogene; genotype; calcitonin; enzyme activity; protein tyrosine kinase; pedigree; oncogene proteins; hyperparathyroidism; thyroid neoplasms; receptor protein-tyrosine kinases; pheochromocytoma; malignant transformation; tyrosine kinase; proto-oncogene proteins c-ret; thyroid tumor; family; proto-oncogenes; calcitonin blood level; multiple endocrine neoplasia; humans; human; male; female; priority journal; article; hirschsprung disease; neurocristopathy; multiple endocrine neoplasia type 2a
Journal Title: Cancer
Volume: 78
Issue: 9
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 1996-11-01
Start Page: 1996
End Page: 2003
Language: English
DOI: 10.1002/(sici)1097-0142(19961101)78:9<1996::aid-cncr22>3.0.co;2-s
PUBMED: 8909322
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 22 November 2017 -- Source: Scopus
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MSK Authors
  1. Murray F Brennan
    743 Brennan
  2. Alexandra B Dimich
    2 Dimich