PMID- 20566584
OWN - NLM
STAT- MEDLINE
DCOM- 20101207
LR  - 20220409
IS  - 1479-6821 (Electronic)
IS  - 1351-0088 (Linking)
VI  - 17
IP  - 3
DP  - 2010 Sep
TI  - MEN1 in pancreatic endocrine tumors: analysis of gene and protein status in 169 
      sporadic neoplasms reveals alterations in the vast majority of cases.
PG  - 771-83
LID - 10.1677/ERC-10-0028 [doi]
AB  - Pancreatic endocrine tumors (PETs) may be part of hereditary multiple endocrine 
      neoplasia type 1 (MEN1) syndrome. While MEN1 gene mutation is the only 
      ascertained genetic anomaly described in PETs, no data exist on the cellular 
      localization of MEN1-encoded protein, menin, in normal pancreas and PETs. A total 
      of 169 PETs were used to assess the i) MEN1 gene mutational status in 100 
      clinically sporadic PETs by direct DNA sequencing, ii) immunohistochemical 
      expression of menin in normal pancreas and 140 PETs, including 71 cases screened 
      for gene mutations, and iii) correlation of these findings with 
      clinical-pathological parameters. Twenty-seven PETs showed mutations that were 
      somatic in 25 patients and revealed to be germline in 2 patients. Menin 
      immunostaining showed strong nuclear and very faint cytoplasmic signal in normal 
      islet cells, whereas it displayed abnormal location and expression levels in 80% 
      of tumors. PETs harboring MEN1 truncating mutations lacked nuclear protein, and 
      most PETs with MEN1 missense mutations showed a strong cytoplasmic positivity for 
      menin. Menin was also misplaced in a significant number of cases lacking MEN1 
      mutations. In conclusion, the vast majority of PETs showed qualitative and/or 
      quantitative alterations in menin localization. In 30% of cases, this was 
      associated with MEN1 mutations affecting sequences involved in nuclear 
      localization or protein-protein interaction. In cases lacking MEN1 mutations, the 
      alteration of one of the menin interactors may have prevented its proper 
      localization, as suggested by recent data showing that menin protein shuttles 
      between the nucleus and cytoplasm and also affects the subcellular localization 
      of its interactors.
FAU - Corbo, Vincenzo
AU  - Corbo V
AD  - ARC-NET Research Center Department of Pathology, University of Verona, 
      Policlinico G.B. Rossi c/o Piastra Odontoiatrica, Piazzale L.A. Scuro 10, Verona, 
      Italy.
FAU - Dalai, Irene
AU  - Dalai I
FAU - Scardoni, Maria
AU  - Scardoni M
FAU - Barbi, Stefano
AU  - Barbi S
FAU - Beghelli, Stefania
AU  - Beghelli S
FAU - Bersani, Samantha
AU  - Bersani S
FAU - Albarello, Luca
AU  - Albarello L
FAU - Doglioni, Claudio
AU  - Doglioni C
FAU - Schott, Christina
AU  - Schott C
FAU - Capelli, Paola
AU  - Capelli P
FAU - Chilosi, Marco
AU  - Chilosi M
FAU - Boninsegna, Letizia
AU  - Boninsegna L
FAU - Becker, Karl-Friedrich
AU  - Becker KF
FAU - Falconi, Massimo
AU  - Falconi M
FAU - Scarpa, Aldo
AU  - Scarpa A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100816
PL  - England
TA  - Endocr Relat Cancer
JT  - Endocrine-related cancer
JID - 9436481
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Adult
MH  - Blotting, Western
MH  - Cell Differentiation
MH  - Female
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics/metabolism/pathology
MH  - Mutation/*genetics
MH  - Pancreatic Neoplasms/*genetics/metabolism/pathology
MH  - Prognosis
MH  - Proto-Oncogene Proteins/*genetics/metabolism
MH  - RNA, Messenger/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2010/06/23 06:00
MHDA- 2010/12/14 06:00
CRDT- 2010/06/23 06:00
PHST- 2010/06/23 06:00 [entrez]
PHST- 2010/06/23 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
AID - ERC-10-0028 [pii]
AID - 10.1677/ERC-10-0028 [doi]
PST - epublish
SO  - Endocr Relat Cancer. 2010 Aug 16;17(3):771-83. doi: 10.1677/ERC-10-0028. Print 
      2010 Sep.