PMID- 28597079
OWN - NLM
STAT- MEDLINE
DCOM- 20180323
LR  - 20181113
IS  - 1432-2307 (Electronic)
IS  - 0945-6317 (Linking)
VI  - 471
IP  - 3
DP  - 2017 Sep
TI  - MEN1 mutations and potentially MEN1-targeting miRNAs are responsible for menin 
      deficiency in sporadic and MEN1 syndrome-associated primary hyperparathyroidism.
PG  - 401-411
LID - 10.1007/s00428-017-2158-3 [doi]
AB  - Inherited, germline mutations of menin-coding MEN1 gene cause multiple endocrine 
      neoplasia type 1 (MEN1), while somatic MEN1 mutations are the sole main driver 
      mutations in sporadic primary hyperparathyroidism (PHPT), suggesting that menin 
      deficiency has a central role in the pathogenesis of PHPT. MiRNAs are small, 
      noncoding RNAs posttranscriptionally regulating gene expression. Our aim was to 
      investigate both the role of MEN1 mutations and potentially MEN1-targeting miRNAs 
      as the underlying cause of menin deficiency in MEN1-associated and sporadic PHPT 
      tissues. Fifty six PHPT tissues, including 16 MEN1-associated tissues, were 
      evaluated. Diagnosis of MEN1 syndrome was based on identification of germline 
      MEN1 mutations. In silico target prediction was used to identify miRNAs 
      potentially targeting MEN1. Menin expression was determined by 
      immunohistochemistry while expression of miRNAs was analyzed by quantitative 
      real-time PCR. Sporadic PHPT tissues were subjected to somatic MEN1 mutation 
      analysis as well. Lack of nuclear menin was identified in all MEN1-associated and 
      in 28% of sporadic PHPT tissues. Somatic MEN1 mutations were found in 25% of 
      sporadic PHPTs. The sensitivity and specificity of menin immunohistochemistry to 
      detect a MEN1 mutation were 86 and 87%, respectively. Expression levels of 
      hsa-miR-24 and hsa-miR-28 were higher in sporadic compared to MEN1-associated 
      PHPT tissues; however, no difference in miRNA levels occurred between 
      menin-positive and menin-negative PHPT tissues. Menin deficiency is the 
      consequence of a MEN1 mutation in most menin-negative PHPT tissues. Elevated 
      expression of hsa-miR-24 and hsa-miR-28 mark the first epigenetic changes 
      observed between sporadic and MEN1-associated PHPT.
FAU - Grolmusz, Vince Kornel
AU  - Grolmusz VK
AUID- ORCID: 0000-0002-5677-895X
AD  - 2nd Department of Medicine, Semmelweis University, Szentkiralyi utca 46, 
      Budapest, 1088, Hungary.
AD  - "Lendulet" Hereditary Endocrine Tumours Research Group, Hungarian Academy of 
      Sciences, Semmelweis University, Szentkiralyi utca 46, Budapest, H-1088, Hungary.
FAU - Borka, Katalin
AU  - Borka K
AD  - 2nd Department of Pathology, Semmelweis University, Ulloi ut 93, Budapest, 1091, 
      Hungary.
FAU - Kovesdi, Annamaria
AU  - Kovesdi A
AD  - 2nd Department of Medicine, Semmelweis University, Szentkiralyi utca 46, 
      Budapest, 1088, Hungary.
FAU - Nemeth, Kinga
AU  - Nemeth K
AD  - 2nd Department of Medicine, Semmelweis University, Szentkiralyi utca 46, 
      Budapest, 1088, Hungary.
FAU - Balogh, Katalin
AU  - Balogh K
AD  - 2nd Department of Medicine, Semmelweis University, Szentkiralyi utca 46, 
      Budapest, 1088, Hungary.
FAU - Dekany, Csaba
AU  - Dekany C
AD  - 2nd Department of Pathology, Semmelweis University, Ulloi ut 93, Budapest, 1091, 
      Hungary.
FAU - Kiss, Andras
AU  - Kiss A
AD  - 2nd Department of Pathology, Semmelweis University, Ulloi ut 93, Budapest, 1091, 
      Hungary.
FAU - Szentpeteri, Anna
AU  - Szentpeteri A
AD  - 2nd Department of Medicine, Semmelweis University, Szentkiralyi utca 46, 
      Budapest, 1088, Hungary.
FAU - Sarman, Beatrix
AU  - Sarman B
AD  - 2nd Department of Medicine, Semmelweis University, Szentkiralyi utca 46, 
      Budapest, 1088, Hungary.
FAU - Somogyi, Aniko
AU  - Somogyi A
AD  - 2nd Department of Medicine, Semmelweis University, Szentkiralyi utca 46, 
      Budapest, 1088, Hungary.
FAU - Csajbok, Eva
AU  - Csajbok E
AD  - 1st Department of Medicine, University of Szeged, Koranyi fasor 8-10, Szeged, 
      6720, Hungary.
FAU - Valkusz, Zsuzsanna
AU  - Valkusz Z
AD  - 1st Department of Medicine, University of Szeged, Koranyi fasor 8-10, Szeged, 
      6720, Hungary.
FAU - Toth, Miklos
AU  - Toth M
AD  - 2nd Department of Medicine, Semmelweis University, Szentkiralyi utca 46, 
      Budapest, 1088, Hungary.
FAU - Igaz, Peter
AU  - Igaz P
AD  - 2nd Department of Medicine, Semmelweis University, Szentkiralyi utca 46, 
      Budapest, 1088, Hungary.
FAU - Racz, Karoly
AU  - Racz K
AD  - 2nd Department of Medicine, Semmelweis University, Szentkiralyi utca 46, 
      Budapest, 1088, Hungary.
AD  - Molecular Medicine Research Group, Hungarian Academy of Sciences, Semmelweis 
      University, Szentkiralyi utca 46, Budapest, 1088, Hungary.
FAU - Patocs, Attila
AU  - Patocs A
AD  - "Lendulet" Hereditary Endocrine Tumours Research Group, Hungarian Academy of 
      Sciences, Semmelweis University, Szentkiralyi utca 46, Budapest, H-1088, Hungary. 
      patocs.attila@med.semmelweis-univ.hu.
AD  - Molecular Medicine Research Group, Hungarian Academy of Sciences, Semmelweis 
      University, Szentkiralyi utca 46, Budapest, 1088, Hungary. 
      patocs.attila@med.semmelweis-univ.hu.
AD  - Department of Laboratory Medicine, Semmelweis University, Nagyvarad ter 4, 
      Budapest, 1089, Hungary. patocs.attila@med.semmelweis-univ.hu.
LA  - eng
GR  - Lendulet 2013/Magyar Tudomanyos Akademia/
GR  - PD100648/Orszagos Tudomanyos Kutatasi Alapprogramok/
PT  - Journal Article
DEP - 20170608
PL  - Germany
TA  - Virchows Arch
JT  - Virchows Archiv : an international journal of pathology
JID - 9423843
RN  - 0 (MEN1 protein, human)
RN  - 0 (MIRN24 microRNA, human)
RN  - 0 (MIRN28 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Germ-Line Mutation
MH  - Humans
MH  - Hyperparathyroidism, Primary/*genetics
MH  - Male
MH  - MicroRNAs/*genetics
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/complications/*genetics
MH  - Proto-Oncogene Proteins/*genetics
OTO - NOTNLM
OT  - Immunohistochemistry
OT  - MEN1
OT  - Menin
OT  - Mutation
OT  - Primary hyperparathyroidism
OT  - microRNA
EDAT- 2017/06/10 06:00
MHDA- 2018/03/24 06:00
CRDT- 2017/06/10 06:00
PHST- 2016/10/31 00:00 [received]
PHST- 2017/05/17 00:00 [accepted]
PHST- 2017/04/24 00:00 [revised]
PHST- 2017/06/10 06:00 [pubmed]
PHST- 2018/03/24 06:00 [medline]
PHST- 2017/06/10 06:00 [entrez]
AID - 10.1007/s00428-017-2158-3 [pii]
AID - 10.1007/s00428-017-2158-3 [doi]
PST - ppublish
SO  - Virchows Arch. 2017 Sep;471(3):401-411. doi: 10.1007/s00428-017-2158-3. Epub 2017 
      Jun 8.