PMID- 11095441
OWN - NLM
STAT- MEDLINE
DCOM- 20001214
LR  - 20061115
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 85
IP  - 11
DP  - 2000 Nov
TI  - Rare somatic inactivation of the multiple endocrine neoplasia type 1 gene in 
      secondary hyperparathyroidism of uremia.
PG  - 4113-7
AB  - The molecular pathway of autonomous growth of the parathyroid glands in uremic 
      patients is poorly understood. Loss of heterozygosity at the recently identified 
      multiple endocrine neoplasia type 1 (MEN1) gene locus on chromosome 11q13 has 
      been found in a subset of parathyroid glands from patients with refractory 
      hyperparathyroidism. To clarify the role of the MEN1 gene in parathyroid 
      tumorigenesis, we analyzed 81 parathyroid glands from 22 Japanese uremic patients 
      for allelic loss on chromosomal arm 11q13 DNA using 3 flanking markers (PYGM, 
      D11S4946, and D11S449) and for mutations of the MEN1-coding exons by PCR-based 
      single strand conformation polymorphism analysis and sequencing. Allelic loss on 
      11q13 was observed in 6 glands (7%), and 1 of 6 demonstrated a previously 
      unrecognized somatic frameshift deletion (331delG) of the MEN1 gene. This 
      mutation would probably result in a nonfunctional menin protein, consistent with 
      a tumor suppressor mechanism. Clinical and pathological characteristics of 
      hyperparathyroidism were unrelated to the presence or absence of loss of 
      heterozygosity on 11q13 and MEN1 gene mutations. These observations indicate that 
      somatic inactivation of the MEN1 gene contributes to the pathogenesis of 
      uremia-associated parathyroid tumors, but its role in this disease appears to be 
      very limited.
FAU - Tahara, H
AU  - Tahara H
AD  - Department of Internal Medicine, Osaka City University Graduate School of 
      Medicine, Japan. hideki-t@ka2.so-net.ne.jp
FAU - Imanishi, Y
AU  - Imanishi Y
FAU - Yamada, T
AU  - Yamada T
FAU - Tsujimoto, Y
AU  - Tsujimoto Y
FAU - Tabata, T
AU  - Tabata T
FAU - Inoue, T
AU  - Inoue T
FAU - Inaba, M
AU  - Inaba M
FAU - Morii, H
AU  - Morii H
FAU - Nishizawa, Y
AU  - Nishizawa Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Genetic Markers)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 11
MH  - Exons
MH  - Female
MH  - *Genes, Tumor Suppressor
MH  - Genetic Markers
MH  - Humans
MH  - Hyperparathyroidism/*etiology/*genetics/pathology
MH  - *Loss of Heterozygosity
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Proteins/*genetics
MH  - Parathyroid Glands/*pathology
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single-Stranded Conformational
MH  - *Proto-Oncogene Proteins
MH  - Uremia/complications/*genetics
EDAT- 2000/11/30 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/11/30 11:00
PHST- 2000/11/30 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/30 11:00 [entrez]
AID - 10.1210/jcem.85.11.6950 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2000 Nov;85(11):4113-7. doi: 10.1210/jcem.85.11.6950.