PMID- 20669561
OWN - NLM
STAT- MEDLINE
DCOM- 20100915
LR  - 20120604
IS  - 0001-4079 (Print)
IS  - 0001-4079 (Linking)
VI  - 194
IP  - 1
DP  - 2010 Jan
TI  - [Multiple endocrine neoplasia: genetic aspects].
PG  - 81-95; discussion 95-6
AB  - Multiple endocrine neoplasia type 1 (MEN1) and type 2 (MEN2) are major genetic 
      disorders carrying a high risk of endocrine tumor development. The mutated genes 
      were identified in 1993 (MEN2-RET) and 1997 (MEN1), enabling genetic testing and 
      functional studies. Genetic analysis has led to new clinical and therapeutic 
      strategies for MEN1/2 patients, and has improved our understanding of the 
      pathways underlying the development of such tumors, which occur in an autosomal 
      dominant manner and with high penetrance. The MEN1 gene encodes menin, a protein 
      involved in many cell functions, such as transcription, genome stability, cell 
      cycling and apoptosis. The MEN1 gene has 10 exons, and its exhaustive analysis in 
      MEN1 patients helps guide their management. MEN2 is related to activating 
      missense mutations in the RET protooncogene, which encodes a tyrosine kinase 
      receptor (TKR). RET activation occurs upon autodimerization induced by the 
      binding of specific ligands belonging to glial cell-derived neurotrophic 
      factor-like family (GFL) proteins, regulated by coreceptors. The position of 
      missense mutations--in the extracellular or intracellular TK domains--influences 
      the aggressiveness of the most frequent malignancy, medullary thyroid carcinoma, 
      establishing a genotype-phenotype correlation. We also briefly describe the 
      genetic basis of three other inherited states predisposing individuals to 
      endocrine tumors, namely Carney's syndrome, hyperparathyroidism type 2 (HRPT2) 
      and familial isolated pituitary adenoma (FIPA), which are related to inactivating 
      mutations in the PRKAR1-alpha, HRPT2 and AIP genes, respectively.
FAU - Calender, Alain
AU  - Calender A
AD  - Genetique Moleculaire et Medicale, Hopital Edouard Herriot, F-69437 - Lyon cedex 
      03. alain.calender@chu-lyon.fr
CN  - Groupe d'etude des Tumeurs Endocrines
LA  - fre
PT  - English Abstract
PT  - Journal Article
PT  - Review
TT  - Neoplasies endocriniennes multiples, aspects genetiques.
PL  - Netherlands
TA  - Bull Acad Natl Med
JT  - Bulletin de l'Academie nationale de medecine
JID - 7503383
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor Receptors)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
RN  - EC 2.7.10.1 (RET protein, human)
SB  - IM
MH  - Animals
MH  - Carcinoma, Medullary/genetics/pathology
MH  - Digestive System Neoplasms/genetics
MH  - Dimerization
MH  - Disease Models, Animal
MH  - Embryonic Development/genetics
MH  - Female
MH  - Genes, Dominant
MH  - *Genes, Tumor Suppressor
MH  - Genetic Testing
MH  - Glial Cell Line-Derived Neurotrophic Factor Receptors/chemistry/metabolism
MH  - Humans
MH  - Mice
MH  - Multiple Endocrine Neoplasia/epidemiology/*genetics
MH  - Mutation, Missense
MH  - Neoplastic Syndromes, Hereditary/genetics
MH  - Pregnancy
MH  - Protein Structure, Tertiary
MH  - Proto-Oncogene Proteins/*genetics/physiology
MH  - Proto-Oncogene Proteins c-ret/*genetics/physiology
MH  - Thyroid Neoplasms/genetics/pathology
RF  - 30
EDAT- 2010/07/31 06:00
MHDA- 2010/09/17 06:00
CRDT- 2010/07/31 06:00
PHST- 2010/07/31 06:00 [entrez]
PHST- 2010/07/31 06:00 [pubmed]
PHST- 2010/09/17 06:00 [medline]
PST - ppublish
SO  - Bull Acad Natl Med. 2010 Jan;194(1):81-95; discussion 95-6.