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 I and intr on 2 polymorphisms. The relationship between LOH and clinicopathologic para meters was assessed. Expression of VHL was investigated by immunohistochemi stry with a VHL-specific antibody. PCR-SSCP analysis of VHL revealed 2 diff erent aberrant patterns in 19 patients. Upon DNA sequencing, I pattern appe ared to be a previously described exon I polymorphism. The other single abe rrant pattern was an intron 2 polymorphism, not yet described. PCR-SSCP ana lysis of PPAR gamma showed no aberrant migration patterns. LOH analysis rev ealed 3p25-26 loss in 24/36 (67%) informative cases, but this was not signi ficantly correlated with clinicopathologic parameters. By immunohistochemis try, 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 o r involvement of another tumor-suppressor gene on 3p as the target of LOH s hould be considered. (C) 2001 Wiley-Liss, Inc.