PMID- 21819486
OWN - NLM
STAT- MEDLINE
DCOM- 20111219
LR  - 20191210
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Linking)
VI  - 102
IP  - 11
DP  - 2011 Nov
TI  - Correlation of mutant menin stability with clinical expression of multiple 
      endocrine neoplasia type 1 and its incomplete forms.
PG  - 2097-102
LID - 10.1111/j.1349-7006.2011.02055.x [doi]
AB  - Germline mutations of the tumor suppressor gene MEN1 are found not only in 
      typical multiple endocrine neoplasia type 1 (MEN1) but also in its incomplete 
      forms such as familial isolated hyperparathyroidism (FIHP) and apparently 
      sporadic parathyroid tumor (ASPT). No definitive genotype-phenotype correlation 
      has been established between these clinical forms and MEN1 gene mutations. We 
      previously demonstrated that mutant menin proteins associated with MEN1 are 
      rapidly degraded by the ubiquitin-proteasome pathway. To examine whether the 
      intracellular stability of mutant menin is correlated with clinical phenotypes, 
      we developed a method of evaluating menin stability and examined 20 mutants 
      associated with typical MEN1 (17 missense, two in-frame deletion, one nonsense) 
      and 21 mutants associated with FIHP or ASPT (19 missense, two in-frame deletion). 
      All tested mutants associated with typical MEN1 showed reduced stability. Some 
      missense and in-frame deletion mutants (G28A, R171W, T197I, E255K, E274A, Y353del 
      and E366D) associated with FIHP or ASPT were almost as stable as or only slightly 
      less stable than wild-type menin, while others were as unstable as those 
      associated with typical MEN1. Some stable mutants exhibited substantial 
      biological activities when tested by JunD-dependent transactivation assay. These 
      findings suggest that certain missense and in-frame mutations are fairly stable 
      and retain intrinsic biological activity, and might be specifically associated 
      with incomplete clinical phenotypes. The menin stability test will provide useful 
      information for the management of patients carrying germline MEN1 mutations 
      especially when they have missense or in-frame variants of ambiguous clinical 
      significance.
CI  - (c) 2011 Japanese Cancer Association.
FAU - Shimazu, Satoko
AU  - Shimazu S
AD  - Division of Familial Cancer Research, National Cancer Center Research Institute, 
      Tokyo, Japan.
FAU - Nagamura, Yuko
AU  - Nagamura Y
FAU - Yaguchi, Hiroko
AU  - Yaguchi H
FAU - Ohkura, Naganari
AU  - Ohkura N
FAU - Tsukada, Toshihiko
AU  - Tsukada T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110901
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (Codon, Nonsense)
RN  - 0 (JunD protein, human)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 0 (Recombinant Fusion Proteins)
SB  - IM
MH  - Amino Acid Substitution
MH  - Animals
MH  - COS Cells
MH  - Cells, Cultured
MH  - Chlorocebus aethiops
MH  - Codon, Nonsense
MH  - Genetic Heterogeneity
MH  - Genotype
MH  - Germ-Line Mutation
MH  - Humans
MH  - Hyperparathyroidism, Primary/*genetics
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - *Mutation
MH  - Mutation, Missense
MH  - Parathyroid Neoplasms/*genetics
MH  - Phenotype
MH  - Point Mutation
MH  - Protein Stability
MH  - Proto-Oncogene Proteins/biosynthesis/chemistry/*genetics
MH  - Proto-Oncogene Proteins c-jun/physiology
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - Sequence Deletion
MH  - Transcriptional Activation
EDAT- 2011/08/09 06:00
MHDA- 2011/12/20 06:00
CRDT- 2011/08/09 06:00
PHST- 2011/08/09 06:00 [entrez]
PHST- 2011/08/09 06:00 [pubmed]
PHST- 2011/12/20 06:00 [medline]
AID - 10.1111/j.1349-7006.2011.02055.x [doi]
PST - ppublish
SO  - Cancer Sci. 2011 Nov;102(11):2097-102. doi: 10.1111/j.1349-7006.2011.02055.x. 
      Epub 2011 Sep 1.