PMID- 8514889
OWN - NLM
STAT- MEDLINE
DCOM- 19930721
LR  - 20181130
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 91
IP  - 6
DP  - 1993 Jun
TI  - Association of somatotrophinomas with loss of alleles on chromosome 11 and with 
      gsp mutations.
PG  - 2815-21
AB  - The molecular pathology of somatotrophinomas has been investigated by a combined 
      search for dominant mutations of the gene encoding the Gs alpha protein and for 
      recessive mutations involving chromosome 11q13, which contains the gene causing 
      multiple endocrine neoplasia type 1 (MEN1). Somatotrophinomas and peripheral 
      leukocytes were obtained from thirteen patients with acromegaly; one patient also 
      suffered from MEN1. Five DNA probes identifying restriction fragment length 
      polymorphisms from 11q revealed allele loss in pituitary tumors from five (four 
      non-MEN1 and one MEN1) patients. Deletion mapping revealed that the region of 
      allele loss common to the somatotrophinomas involved 11q13. An analysis for 
      similar allelic deletions at 12 other loci from chromosomes 1-5, 7-9, 12-14, and 
      17 did not reveal generalized allele loss in the somatotrophinomas. These 
      results, which represent the first report of chromosome 11 allele loss occurring 
      in non-MEN1 somatotrophinomas, indicate that a recessive oncogene on 11q13 is 
      specifically involved in the monoclonal development of somatotrophinomas. In 
      addition Gs alpha mutations were detected in two non-MEN1 somatotrophinomas, one 
      of which also revealed allele loss of chromosome 11. Thus, our results reveal 
      that the development of somatotrophinomas is associated with alterations in both 
      dominant and recessive oncogenes and further characterization of these genetic 
      abnormalities will help to elucidate the multistep etiology and progression of 
      somatotrophinomas.
FAU - Thakker, R V
AU  - Thakker RV
AD  - M.R.C. Molecular Medicine Group, Royal Postgraduate Medical School, Hammersmith 
      Hospital, London, United Kingdom.
FAU - Pook, M A
AU  - Pook MA
FAU - Wooding, C
AU  - Wooding C
FAU - Boscaro, M
AU  - Boscaro M
FAU - Scanarini, M
AU  - Scanarini M
FAU - Clayton, R N
AU  - Clayton RN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 9002-72-6 (Growth Hormone)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
GS  - gsp
MH  - Acromegaly/genetics
MH  - Adult
MH  - Aged
MH  - *Alleles
MH  - Base Sequence
MH  - *Chromosome Deletion
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 11
MH  - Female
MH  - GTP-Binding Proteins/*genetics
MH  - Genes, Dominant/genetics
MH  - Genes, Recessive/genetics
MH  - Genes, Suppressor/genetics
MH  - Growth Hormone/*metabolism
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Oncogenes/genetics
MH  - Pituitary Neoplasms/*genetics
PMC - PMC443349
EDAT- 1993/06/01 00:00
MHDA- 1993/06/01 00:01
PMCR- 1993/06/01
CRDT- 1993/06/01 00:00
PHST- 1993/06/01 00:00 [pubmed]
PHST- 1993/06/01 00:01 [medline]
PHST- 1993/06/01 00:00 [entrez]
PHST- 1993/06/01 00:00 [pmc-release]
AID - 10.1172/JCI116524 [doi]
PST - ppublish
SO  - J Clin Invest. 1993 Jun;91(6):2815-21. doi: 10.1172/JCI116524.