Germline and somatic mutation of the gene for multiple endocrine neoplasia type 1 (MEN1).
Dideoxyfingerprinting was used to screen for germline and somatic MEN1 mutations. This method, applied to a panel of germline DNA from 15 probands with multiple endocrine neoplasia type 1 (MEN-1), allowed confident discovery of the MEN1 gene. Germline MEN1 mutation has been found in 47 out of 50 probands with familial MEN-1, in 7 out of 8 cases with sporadic MEN-1, and in 1 out of 3 cases with atypical sporadic MEN-1. Germline MEN1 mutation was not found in any of five probands with familial hyperparathyroidism. Somatic MEN1 mutations were found in 7 out of 33 parathyroid tumours not associated with MEN-1. Allowing for repeating mutations, a total of 47 different germline or somatic MEN1 mutations have been identified. Most predict inactivation of the encoded 'menin' protein. supporting expectations that MEN1 is a tumour suppressor gene. The 16 observed missense mutations were distributed across the gene, suggesting that many domains are important to its as yet unknown functions.
Marx
S J
SJ
Metabolic Diseases Branch, NIDDK, National Institutes of Health, Bethesda, MD 20892-1802, USA. StephenM@ambintra.niddk.nih.gov
Agarwal
S K
SK
Kester
M B
MB
Heppner
C
C
Kim
Y S
YS
Emmert-Buck
M R
MR
Debelenko
L V
LV
Lubensky
I A
IA
Zhuang
Z
Z
Guru
S C
SC
Manickam
P
P
Olufemi
S E
SE
Skarulis
M C
MC
Doppman
J L
JL
Alexander
R H
RH
Liotta
L A
LA
Collins
F S
FS
Chandrasekharappa
S C
SC
Spiegel
A M
AM
Burns
A L
AL
D003062:Codon / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000235:genetics; D018095:Germ-Line Mutation; D006801:Humans; D006961:Hyperparathyroidism / Q000235:genetics; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D010282:Parathyroid Neoplasms / Q000235:genetics
D003062:Codon; D004273:DNA, Neoplasm