PMID- 9241276
OWN - NLM
STAT- MEDLINE
DCOM- 19970828
LR  - 20061115
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 16
IP  - 4
DP  - 1997 Aug
TI  - Somatic mutation of the MEN1 gene in parathyroid tumours.
PG  - 375-8
AB  - Primary hyperparathyroidism is a common disorder with an annual incidence of 
      approximately 0.5 in 1,000 (ref. 1). In more than 95% of cases, the disease is 
      caused by sporadic parathyroid adenoma or sporadic hyperplasia. Some cases are 
      caused by inherited syndromes, such as multiple endocrine neoplasia type 1 (MEN1; 
      ref. 2). In most cases, the molecular basis of parathyroid neoplasia is unknown. 
      Parathyroid adenomas are usually monoclonal, suggesting that one important step 
      in tumour development is a mutation in a progenitor cell. Approximately 30% of 
      sporadic parathyroid tumours show loss of heterozygosity (LOH) for polymorphic 
      markers on 11q13, the site of the MEN1 tumour suppressor gene. This raises the 
      question of whether such sporadic parathyroid tumours are caused by sequential 
      inactivation of both alleles of the MEN1 gene. We recently cloned the MEN1 gene 
      and identified MEN1 germline mutations in fourteen of fifteen kindreds with 
      familial MEN1 (ref. 10). We have studied parathyroid tumours not associated with 
      MEN1 to determine whether somatic mutations in the MEN1 gene are present. Among 
      33 tumours we found somatic MEN1 gene mutation in 7, while the corresponding MEN1 
      germline sequence was normal in each patient. All tumours with MEN1 gene mutation 
      showed LOH on 11q13, making the tumour cells hemi- or homozygous for the mutant 
      allele. Thus, somatic MEN1 gene mutation for the mutant allele. Thus, somatic 
      MEN1 gene mutation contributes to tumorigenesis in a substantial number of 
      parathyroid tumours not associated with the MEN1 syndrome.
FAU - Heppner, C
AU  - Heppner C
AD  - Metabolic Diseases Branch, National Institute of Diabetes and Digestive and 
      Kidney Diseases, NIH, Bethesda, Maryland 20892, USA.
FAU - Kester, M B
AU  - Kester MB
FAU - Agarwal, S K
AU  - Agarwal SK
FAU - Debelenko, L V
AU  - Debelenko LV
FAU - Emmert-Buck, M R
AU  - Emmert-Buck MR
FAU - Guru, S C
AU  - Guru SC
FAU - Manickam, P
AU  - Manickam P
FAU - Olufemi, S E
AU  - Olufemi SE
FAU - Skarulis, M C
AU  - Skarulis MC
FAU - Doppman, J L
AU  - Doppman JL
FAU - Alexander, R H
AU  - Alexander RH
FAU - Kim, Y S
AU  - Kim YS
FAU - Saggar, S K
AU  - Saggar SK
FAU - Lubensky, I A
AU  - Lubensky IA
FAU - Zhuang, Z
AU  - Zhuang Z
FAU - Liotta, L A
AU  - Liotta LA
FAU - Chandrasekharappa, S C
AU  - Chandrasekharappa SC
FAU - Collins, F S
AU  - Collins FS
FAU - Spiegel, A M
AU  - Spiegel AM
FAU - Burns, A L
AU  - Burns AL
FAU - Marx, S J
AU  - Marx SJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (DNA, Neoplasm)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Chromosomes, Human, Pair 11
MH  - DNA Fingerprinting
MH  - DNA Mutational Analysis
MH  - DNA, Neoplasm/analysis
MH  - Gene Deletion
MH  - Heterozygote
MH  - Humans
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - *Mutation
MH  - Neoplasm Proteins/*genetics
MH  - Parathyroid Neoplasms/*genetics
MH  - *Proto-Oncogene Proteins
EDAT- 1997/08/01 00:00
MHDA- 1997/08/01 00:01
CRDT- 1997/08/01 00:00
PHST- 1997/08/01 00:00 [pubmed]
PHST- 1997/08/01 00:01 [medline]
PHST- 1997/08/01 00:00 [entrez]
AID - 10.1038/ng0897-375 [doi]
PST - ppublish
SO  - Nat Genet. 1997 Aug;16(4):375-8. doi: 10.1038/ng0897-375.