PMID- 33919851
OWN - NLM
STAT- MEDLINE
DCOM- 20210513
LR  - 20231103
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 8
DP  - 2021 Apr 14
TI  - Pancreatic Neuroendocrine Neoplasms in Multiple Endocrine Neoplasia Type 1.
LID - 10.3390/ijms22084041 [doi]
LID - 4041
AB  - Pancreatic neuroendocrine tumors (pNETs) are a rare group of cancers accounting 
      for about 1-2% of all pancreatic neoplasms. About 10% of pNETs arise within 
      endocrine tumor syndromes, such as Multiple Endocrine Neoplasia type 1 (MEN1). 
      pNETs affect 30-80% of MEN1 patients, manifesting prevalently as multiple 
      microadenomas. pNETs in patients with MEN1 are particularly difficult to treat 
      due to differences in their growth potential, their multiplicity, the frequent 
      requirement of extensive surgery, the high rate of post-operative recurrences, 
      and the concomitant development of other tumors. MEN1 syndrome is caused by 
      germinal heterozygote inactivating mutation of the MEN1 gene, encoding the menin 
      tumor suppressor protein. MEN1-related pNETs develop following the complete loss 
      of function of wild-type menin. Menin is a key regulator of endocrine cell 
      plasticity and its loss in these cells is sufficient for tumor initiation. 
      Somatic biallelic loss of wild-type menin in the neuroendocrine pancreas 
      presumably alters the epigenetic control of gene expression, mediated by histone 
      modifications and DNA hypermethylation, as a driver of MEN1-associated pNET 
      tumorigenesis. In this light, epigenetic-based therapies aimed to correct the 
      altered DNA methylation, and/or histone modifications might be a possible 
      therapeutic strategy for MEN1 pNETs, for whom standard treatments fail.
FAU - Marini, Francesca
AU  - Marini F
AD  - Department of Experimental and Clinical Biomedical Sciences, University of 
      Florence, Viale Pieraccini 6, 50139 Florence, Italy.
AD  - F.I.R.M.O. Italian Foundation for the Research on Bone Diseases, Via Reginaldo 
      Giuliani 195/A, 50141 Florence, Italy.
FAU - Giusti, Francesca
AU  - Giusti F
AUID- ORCID: 0000-0002-8576-9606
AD  - Department of Experimental and Clinical Biomedical Sciences, University of 
      Florence, Viale Pieraccini 6, 50139 Florence, Italy.
FAU - Tonelli, Francesco
AU  - Tonelli F
AD  - F.I.R.M.O. Italian Foundation for the Research on Bone Diseases, Via Reginaldo 
      Giuliani 195/A, 50141 Florence, Italy.
FAU - Brandi, Maria Luisa
AU  - Brandi ML
AD  - F.I.R.M.O. Italian Foundation for the Research on Bone Diseases, Via Reginaldo 
      Giuliani 195/A, 50141 Florence, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210414
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
SB  - IM
MH  - Animals
MH  - Epigenesis, Genetic
MH  - Humans
MH  - Multiple Endocrine Neoplasia Type 1/classification/genetics/*pathology/therapy
MH  - Neuroendocrine Tumors/classification/genetics/*pathology/therapy
MH  - Pancreatic Neoplasms/classification/genetics/*pathology/therapy
MH  - Signal Transduction/genetics
PMC - PMC8070788
OTO - NOTNLM
OT  - MEN1 gene
OT  - Multiple Endocrine Neoplasia type 1 (MEN1)
OT  - epigenetic factors
OT  - gene mutation
OT  - menin
OT  - pancreatic neuroendocrine tumors (pNETs)
COIS- All the authors declare that they have no conflict of interest.
EDAT- 2021/05/01 06:00
MHDA- 2021/05/14 06:00
PMCR- 2021/04/14
CRDT- 2021/04/30 01:13
PHST- 2021/03/31 00:00 [received]
PHST- 2021/04/12 00:00 [revised]
PHST- 2021/04/12 00:00 [accepted]
PHST- 2021/04/30 01:13 [entrez]
PHST- 2021/05/01 06:00 [pubmed]
PHST- 2021/05/14 06:00 [medline]
PHST- 2021/04/14 00:00 [pmc-release]
AID - ijms22084041 [pii]
AID - ijms-22-04041 [pii]
AID - 10.3390/ijms22084041 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Apr 14;22(8):4041. doi: 10.3390/ijms22084041.