PMID- 11580998
OWN - NLM
STAT- MEDLINE
DCOM- 20011204
LR  - 20190906
IS  - 0804-4643 (Print)
IS  - 0804-4643 (Linking)
VI  - 145
IP  - 4
DP  - 2001 Oct
TI  - Homozygous inactivation of the MEN1 gene as a specific somatic event in a case of 
      secondary hyperparathyroidism.
PG  - 415-20
AB  - BACKGROUND: Most patients who have been surgically treated for secondary 
      hyperparathyroidism (HPT) harbor at least one pathological parathyroid gland with 
      a tumor of monoclonal origin. OBJECTIVE: To elucidate the underlying genetic 
      mechanisms behind secondary HPT, by studying a panel of such tumors for numerical 
      alterations. METHODS: Sixteen parathyroid glands from eight patients (median age 
      58 years, range 31-74 years), were screened for numerical chromosomal imbalances, 
      using comparative genomic hybridization (CGH). Mutation analysis of the multiple 
      endocrine neoplasia type 1 gene (MEN1) was also performed by sequencing of the 
      coding region. RESULTS: The results show that gross chromosomal alterations occur 
      rarely in secondary HPT. In one of the three glands analyzed from one patient, a 
      complete loss of chromosome 11 was detected. This gland also had an inactivating 
      nonsense mutation, E469X, of the MEN1 gene. The mutation was present neither in 
      the other two glands, nor in the constitutional tissue of the same patient, thus 
      confirming its somatic origin. CONCLUSIONS: The relative lack of numerical 
      chromosomal alterations would suggest that more discrete genetic alterations are 
      responsible for the monoclonal growth in the majority of cases of secondary HPT. 
      Furthermore, somatic inactivation of the MEN1 tumor suppressor gene contributes 
      to the tumorigenesis in a small proportion of the cases.
FAU - Forsberg, L
AU  - Forsberg L
AD  - Department of Molecular Medicine, Endocrine Tumor Unit, Karolinska Hospital CMM 
      L8:01, SE-171 76 Stockholm, Sweden. lars.forsberg@cmm.ki.se
FAU - Villablanca, A
AU  - Villablanca A
FAU - Valimaki, S
AU  - Valimaki S
FAU - Farnebo, F
AU  - Farnebo F
FAU - Farnebo, L O
AU  - Farnebo LO
FAU - Lagercrantz, S
AU  - Lagercrantz S
FAU - Larsson, C
AU  - Larsson C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Endocrinol
JT  - European journal of endocrinology
JID - 9423848
RN  - 0 (Codon, Nonsense)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Base Sequence/genetics
MH  - Chromosomes, Human, Pair 11
MH  - Codon, Nonsense
MH  - Female
MH  - Gene Deletion
MH  - *Gene Silencing
MH  - *Homozygote
MH  - Humans
MH  - Hyperparathyroidism, Secondary/*genetics
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Proteins/*genetics
MH  - Nucleic Acid Hybridization
MH  - *Proto-Oncogene Proteins
EDAT- 2001/10/03 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/10/03 10:00
PHST- 2001/10/03 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/10/03 10:00 [entrez]
AID - 1450415 [pii]
AID - 10.1530/eje.0.1450415 [doi]
PST - ppublish
SO  - Eur J Endocrinol. 2001 Oct;145(4):415-20. doi: 10.1530/eje.0.1450415.