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. 2017 Feb;27(2):215-223.
doi: 10.1089/thy.2016.0411. Epub 2017 Jan 13.

Distribution of RET Mutations in Multiple Endocrine Neoplasia 2 in Denmark 1994-2014: A Nationwide Study

Jes Sloth Mathiesen  1   2 , Jens Peter Kroustrup  3 , Peter Vestergaard  3 , Kirstine Stochholm  4 , Per Løgstrup Poulsen  4 , Åse Krogh Rasmussen  5 , Ulla Feldt-Rasmussen  5 , Mette Gaustadnes  6 , Torben Falck Ørntoft  6 , Thomas van Overeem Hansen  7 , Finn Cilius Nielsen  7 , Kim Brixen  8 , Christian Godballe  1 , Anja Lisbeth Frederiksen  9
Affiliations

Distribution of RET Mutations in Multiple Endocrine Neoplasia 2 in Denmark 1994-2014: A Nationwide Study

Jes Sloth Mathiesen et al. Thyroid. 2017 Feb.

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.

Keywords: epidemiology; genetics; medullary thyroid carcinoma; medullary thyroid carcinoma—genetics; molecular biology.

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Conflict of interest statement

The authors declare that no competing financial interests exist.

Figures

<b>FIG. 1.</b>
FIG. 1.
Flow chart showing patients and families tested for REarranged during Transfection (RET) mutations in Denmark 1994–2014. The Center for Genomic Medicine, Department of Molecular Medicine, and Department of Endocrinology and Medicine are part of Copenhagen University Hospital, Aarhus University Hospital, and Aalborg University Hospital, respectively.
See this image and copyright information in PMC

References

    1. Wells SA, Jr, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, Lee N, Machens A, Moley JF, Pacini F, Raue F, Frank-Raue K, Robinson B, Rosenthal MS, Santoro M, Schlumberger M, Shah M, Waguespack SG. 2015. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 25:567–610 - PMC - PubMed
    1. Mulligan LM, Kwok JB, Healey CS, Elsdon MJ, Eng C, Gardner E, Love DR, Mole SE, Moore JK, Papi L. 1993. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature 363:458–460 - PubMed
    1. Donis-Keller H, Dou S, Chi D, Carlson KM, Toshima K, Lairmore TC, Howe JR, Moley JF, Goodfellow P, Wells SA., Jr 1993. Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC. Hum Mol Genet 2:851–856 - PubMed
    1. Hofstra RM, Landsvater RM, Ceccherini I, Stulp RP, Stelwagen T, Luo Y, Pasini B, Hoppener JW, van Amstel HK, Romeo G, Lips CJ, Buys CH. 1994. A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma. Nature 367:375–376 - PubMed
    1. Carlson KM, Dou S, Chi D, Scavarda N, Toshima K, Jackson CE, Wells SA, Jr, Goodfellow PJ, Donis-Keller H. 1994. Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B. Proc Natl Acad Sci U S A 91:1579–1583 - PMC - PubMed

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