Molecular genetic analysis of the von Hippel-Lindau and human peroxisome proliferator-activated receptor gamma tumor-suppressor genes in adenocarcinomas of the gastroesophageal junction.
We investigated whether 2 candidate tumor-suppressor genes, VHL at 3p25-26 and PPAR gamma at 3p24.2-25, are involved in GEJ adenocarcinogenesis. In 43 GEJ tumor samples from 40 patients, the entire coding sequence of the VHL gene and the 5' and part of the 3' UTR as well as exons 3 and 5 of the PPAR gamma gene were screened by PCR-SSCP analysis. LOH at 3p25-26 was analyzed with 2 polymorphic microsatellite markers and with the VHL exon 1 and intron 2 polymorphisms. The relationship between LOH and clinicopathologic parameters was assessed. Expression of VHL was investigated by immunohistochemistry with a VHL-specific antibody. PCR-SSCP analysis of VHL revealed 2 different aberrant patterns in 19 patients. Upon DNA sequencing, 1 pattern appeared to be a previously described exon 1 polymorphism. The other single aberrant pattern was an intron 2 polymorphism, not yet described. PCR-SSCP analysis of PPAR gamma showed no aberrant migration patterns. LOH analysis revealed 3p25-26 loss in 24/36 (67%) informative cases, but this was not significantly correlated with clinicopathologic parameters. By immunohistochemistry, all tumors showed expression of VHL protein. Despite the very frequent LOH of 3p in GEJ adenocarcinomas, mutations in VHL and PPAR gamma were not detected. Mutations outside the screened sequences, a gene dosage effect or involvement of another tumor-suppressor gene on 3p as the target of LOH should be considered.
Wijnhoven
B P
BP
Department of Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands.
Lindstedt
E W
EW
Abbou
M
M
Ijzendoorn
Y
Y
de Krijger
R R
RR
Tilanus
H W
HW
Dinjens
W N
WN
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008025:Ligases / Q000235:genetics*; D019656:Loss of Heterozygosity; D018807:Polymorphism, Single-Stranded Conformational; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein
D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human