Exhaustive Studies on Genomic Changes in Gastric Cancer and Precancerous COnditions

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The original aim of this study was to investigate genomic changes in gastric cancer and precancerous gastric epithelium. However, we focused on the changes in gastric cancer because we could not find changes typical to the latter. Changes in the copy number of genes were exhaustively evaluated with oligonucleotide microarray that covered 50k SNP loci in 34 human gastric cancer cell lines. Homozygous deletion was found at 26 loci in a total of 26 cell lines. Copy number amplification was found much more often, and high-grade amplification, more than five copies in at least two cell lines, was found at 31 loci in a total of 20 cell lines. About one half of these loci were not previously reported in gastric cancer. Among the genes contained in these regions, 10 genes and 4 genes were selected for the examination of copy number amplification and that of loss of heterozygosity (LOH), respectively. Cancer tissue was separated from human gastric cancer specimens by using laser microdissection, and the changes in the genes were analyzed with quantitative real-time PCR and evaluation of microsatellite markers, which were found to be frequent also in human gastric cancer tissues. By comparing with clinical data, copy number amplification and LOH were more frequently found in advanced cases with lymph node metastasis or vascular invasion. Those genes the association of which with gastric cancer was found in the current study may play a role in gastric carcinogenesis. In addition, frequent LOH in cases at Stage I/II was significantly associated with shorter overall survival. Determination of LOH of certain genes may be useful in differentiating high-risk patients.