title: Genetic and epigenetic analysis in korean patients with multiple endocrine neoplasia type 1.
abstract: BACKGROUND
  Multiple endocrine neoplasia type 1 (MEN1) is a familial syndrome characterized by the parathyroid, pancreas and pituitary tumors. Parathyroid tumors are the most common clinical manifestations, occurring in more than 90% of MEN1 patients. Heterozygous germline mutations of the MENIN gene underlie the tumorigenesis in MEN1 and epigenetic alterations along with germline mutations may contribute to tumorigenesis. Here, we investigated the associations between genotype and phenotype in Korean MEN1 patients.
  
  
  METHODS
  We analyzed medical records from 14 unrelated MEN1 patients who had newly confirmed MENIN germline mutations, together with 14 previous reports in Korea. Aberrant DNA methylations were also examined in MEN1-related parathyroid tumors using the Infinium HumanMethylation 450 BeadChip.
  
  
  RESULTS
  Total 28 germline mutations of MENIN were relatively highly concentrated in exons 7 and 8 compared to previous reports from Western countries. Six mutations (c.111dupT/p.S38Ffs(*)79, c.225_226insT/p.T76Yfs(*)41, c.383_398del16/p.S128Tfs(*)52, c.746dupT/p.H250Afs(*)20, c.1150G>T/p.E384(*), and c.1508G>A/p.G503N) were newly found in the present study. Of interest, four patients (15%) showed unusual initial presentations and three patients were diagnosed incidentally at the general medical checkup. We also found three distinct sites in exon 2 of MENIN were significantly hypomethylated in the MEN1 parathyroid tumors, comparing correspondent blood samples.
  
  
  CONCLUSIONS
  We also have found a lack of genotype/phenotype correlation in Korean MEN1 patients. There were not a few unusual initial manifestations in MEN1 patients, thus, genetic testing for the MENIN germline mutations can provide important information for the better prognosis. Further studies are warranted to investigate altered DNA methylations in the MENIN gene involved in tumorigenesis.
authors.affiliation: Department of Internal Medicine, Endocrine Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. ; Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yoon Jung
authors.initials: YJ
authors.lastname: Chung
authors.affiliation: Department of Internal Medicine, Endocrine Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sena
authors.initials: S
authors.lastname: Hwang
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jong Ju
authors.initials: JJ
authors.lastname: Jeong
authors.affiliation: Department of Internal Medicine, Endocrine Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sun Yong
authors.initials: SY
authors.lastname: Song
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Endocrine Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. ; Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yumie
authors.initials: Y
authors.lastname: Rhee
keywords: DNA methylation; Germ-line mutation; Korea; Multiple endocrine neoplasia type 1