PMID- 25309785
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20141013
LR  - 20211021
IS  - 2093-596X (Print)
IS  - 2093-5978 (Electronic)
IS  - 2093-596X (Linking)
VI  - 29
IP  - 3
DP  - 2014 Sep
TI  - Genetic and epigenetic analysis in korean patients with multiple endocrine 
      neoplasia type 1.
PG  - 270-9
LID - 10.3803/EnM.2014.29.3.270 [doi]
AB  - 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. CONCLUSION: 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.
FAU - Chung, Yoon Jung
AU  - Chung YJ
AD  - 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.
FAU - Hwang, Sena
AU  - Hwang S
AD  - Department of Internal Medicine, Endocrine Research Institute, Severance 
      Hospital, Yonsei University College of Medicine, Seoul, Korea.
FAU - Jeong, Jong Ju
AU  - Jeong JJ
AD  - Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
FAU - Song, Sun Yong
AU  - Song SY
AD  - Department of Internal Medicine, Endocrine Research Institute, Severance 
      Hospital, Yonsei University College of Medicine, Seoul, Korea.
FAU - Kim, Se Hoon
AU  - Kim SH
AD  - Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
FAU - Rhee, Yumie
AU  - Rhee Y
AD  - 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.
LA  - eng
PT  - Journal Article
DEP - 20140925
PL  - Korea (South)
TA  - Endocrinol Metab (Seoul)
JT  - Endocrinology and metabolism (Seoul, Korea)
JID - 101554139
PMC - PMC4192817
OTO - NOTNLM
OT  - DNA methylation
OT  - Germ-line mutation
OT  - Korea
OT  - Multiple endocrine neoplasia type 1
COIS- No potential conflict of interest relevant to this article was reported.
EDAT- 2014/10/14 06:00
MHDA- 2014/10/14 06:01
PMCR- 2014/09/01
CRDT- 2014/10/14 06:00
PHST- 2013/10/23 00:00 [received]
PHST- 2013/10/29 00:00 [revised]
PHST- 2013/10/31 00:00 [accepted]
PHST- 2014/10/14 06:00 [entrez]
PHST- 2014/10/14 06:00 [pubmed]
PHST- 2014/10/14 06:01 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - 10.3803/EnM.2014.29.3.270 [doi]
PST - ppublish
SO  - Endocrinol Metab (Seoul). 2014 Sep;29(3):270-9. doi: 10.3803/EnM.2014.29.3.270. 
      Epub 2014 Sep 25.