PMID- 11034099
OWN - NLM
STAT- MEDLINE
DCOM- 20001027
LR  - 20041117
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 60
IP  - 19
DP  - 2000 Oct 1
TI  - Survey of genetic alterations in gastrinomas.
PG  - 5536-42
AB  - Gastrinomas are rare gastrin-secreting endocrine tumors that usually arise in the 
      duodenum or pancreas and, if untreated, can cause severe peptic ulcers or 
      metastatic disease. Although most tumors are sporadic they are especially common 
      in patients with multiple endocrine neoplasia type 1 (MEN1), and most studies of 
      these tumors have focused on the role of the MEN1 gene. Although the gene is 
      commonly altered in sporadic tumors, this finding is not universal, and it is 
      highly likely that other genetic defects play a significant role. In the present 
      study, an in-depth analysis of the DNA of eight tumors was carried out in an 
      effort to localize these areas. The experiments consisted of an analysis of 400 
      microsatellite marker loci distributed evenly throughout the human genome, and 
      the results were confirmed with comparative genomic hybridization. Whereas 
      deletions encompassing the MEN1 gene were seen in two tumors, the most striking 
      result was multiple large rearrangements on chromosome 1 in two of the tumors 
      with hepatic metastases. In several instances, an individual tumor had 
      abnormalities of every informative maker on a given chromosome, presumably as a 
      result of aneuploidy affecting that chromosome. Such defects were only seen in 
      the four large or aggressive tumors, and the total number of chromosomes affected 
      in a tumor ranged from 1 to a high of 13 in a patient who had an unusually 
      aggressive tumor This tumor also showed microsatellite instability, and this is 
      the first report of such a defect in gastrinomas. This study implicates 
      chromosome 1 defects, aneuploidy, and perhaps mismatch repair defects as importan 
      features of gastrinomas; deletions involving the MEN1 gene were con firmed, but 
      the rest of the genome was free of large deletions or amplifications.
FAU - Yu, F
AU  - Yu F
AD  - Digestive Diseases Branch, National Institute of Diabetes and Digestive and 
      Kidney Diseases, NIH, Bethesda, Maryland 20892, USA.
FAU - Jensen, R T
AU  - Jensen RT
FAU - Lubensky, I A
AU  - Lubensky IA
FAU - Mahlamaki, E H
AU  - Mahlamaki EH
FAU - Zheng, Y L
AU  - Zheng YL
FAU - Herr, A M
AU  - Herr AM
FAU - Ferrin, L J
AU  - Ferrin LJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (DNA, Neoplasm)
SB  - IM
MH  - Allelic Imbalance
MH  - Aneuploidy
MH  - Chromosome Aberrations
MH  - Chromosomes, Human, Pair 1
MH  - Chromosomes, Human, Pair 11
MH  - Chromosomes, Human, Pair 5
MH  - DNA, Neoplasm/analysis/genetics
MH  - Duodenal Neoplasms/*genetics/pathology
MH  - Gastrinoma/*genetics
MH  - Genome, Human
MH  - Humans
MH  - Lymphatic Metastasis
MH  - Microsatellite Repeats
MH  - Nucleic Acid Hybridization
MH  - Pancreatic Neoplasms/*genetics/pathology
MH  - Polymerase Chain Reaction
EDAT- 2000/10/18 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/10/18 11:00
PHST- 2000/10/18 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/10/18 11:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2000 Oct 1;60(19):5536-42.