1. Distribution of RET Mutations in Multiple Endocrine Neoplasia 2 in Denmark 1994–2014: A Nationwide Study
- Author
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Åse Krogh Rasmussen, Peter Vestergaard, Jens Peter Kroustrup, Kim Brixen, Mette Gaustadnes, Kirstine Stochholm, Torben F. Ørntoft, Jes Sloth Mathiesen, Ulla Feldt-Rasmussen, Finn Cilius Nielsen, Per Løgstrup Poulsen, Thomas van Overeem Hansen, Christian Godballe, and Anja Lisbeth Frederiksen
- Subjects
Multiple Endocrine Neoplasia Type 2b/genetics ,Denmark ,Endocrinology, Diabetes and Metabolism ,Multiple Endocrine Neoplasia Type 2a ,030209 endocrinology & metabolism ,Multiple Endocrine Neoplasia Type 2b ,Biology ,Proto-Oncogene Mas ,White People ,Multiple Endocrine Neoplasia Type 2a/genetics ,03 medical and health sciences ,Exon ,symbols.namesake ,0302 clinical medicine ,Endocrinology ,Germline mutation ,medullary thyroid carcinoma ,Journal Article ,medicine ,molecular biology ,Humans ,genetics ,European Continental Ancestry Group/genetics ,Multiple endocrine neoplasia ,Germ-Line Mutation ,Retrospective Studies ,Genetics ,Sanger sequencing ,medullary thyroid carcinoma-genetics ,Proto-Oncogene Proteins c-ret ,Retrospective cohort study ,Thyroid Cancer and Nodules ,Proto-Oncogene Proteins c-ret/genetics ,medicine.disease ,Founder Effect ,medullary thyroid carcinoma—genetics ,030220 oncology & carcinogenesis ,symbols ,epidemiology ,Founder effect ,Multiple endocrine neoplasia type 2b - Abstract
BACKGROUND: Germline mutations of the REarranged during Transfection (RET) proto-oncogene cause multiple endocrine neoplasia 2 (MEN2). It is unclear whether the distribution of RET mutations varies among populations. The first nationwide study of the distribution of RET mutations was conducted, and the results were compared to those of other populations.METHODS: This retrospective cohort study included 1583 patients who underwent RET gene testing in one of three centers covering all of Denmark between September 1994 and December 2014. Primary testing method was Sanger sequencing, which included exons 8-11 and 13-16. Mutations were defined according to the ARUP database July 1, 2016.RESULTS: RET mutations were identified in 163 patients from 36 apparently unrelated families. Among the 36 families 13 (36.1%) carried mutations in codon 611, four (11.1%) in codon 618, three (8.3%) in codon 620, one (2.8%) in codon 631, six (16.7%) in codon 634, one (2.8%) in codon 790, one (2.8%) in codon 804, one (2.8%) in codon 852, one (2.8%) in codon 883, and five (13.9%) in codon 918. Among the 13 families with codon 611 mutations, 12 had the p.C611Y mutation.CONCLUSIONS: The distribution of RET mutations in Denmark appears to differ from that of other populations. Mutations in codon 611 were the most prevalent, followed by more frequently reported mutations. This might be due to a possible founder effect for the p.C611Y mutation. However, further studies are needed to find possible explanations for the skewed mutational spectrum in Denmark.
- Published
- 2017