Distribution ofRETMutations in Multiple Endocrine Neoplasia 2 in Denmark 1994–2014: A Nationwide Study

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.

Incidence and prevalence of multiple endocrine neoplasia 2B in Denmark: a nationwide study

“…This retrospective cohort study included 12 unique MEN2B patients identified through the following sources: 1. A nationwide RET cohort containing all patients (n = 1583) RET tested in Denmark from 1994 to 2014 (Mathiesen et al 2017b). Eight MEN2B patients were identified from this source.…”

Long‐term follow‐up of RET Y791F carriers in Denmark 1994‐2017: A National Cohort Study

“…An original national cohort comprising all patients tested for RET mutations in Denmark from September 1994 to December 2014 was extended to October 2017 . This combined cohort was then searched for carriers of RET Y791F.…”

“…Carriers were excluded if harboring an additional RET variant acknowledged as pathogenic in the ARUP MEN2 database as per October 1st, 2018 . The methods of genomic testing have been previously reported and still apply …”

Completeness of<em> RET</em> testing in patients with medullary thyroid carcinoma in Denmark 1997&ndash;2013: a nationwide study

“…In Denmark, RET testing has been available since September 1994. 8 Seven years later, in February 2002, the first Danish guidelines, recommending RET testing of all patients with MTC, were published. 9 In the meantime, it is unknown if these guidelines have improved completeness of RET testing in MTC patients.…”