FRACTIONAL ALLELIC LOSS IN GASTRIC-CARCINOMA CORRELATES WITH GROWTH-PATTERNS

To gain an insight into the genetic events underlying morphological ph enotypes, we analysed 58 gastric carcinoma tissues for the genome-wide allelotype study using microsatellite markers. Based on a binomial di stribution, loss of heterozygosity (LOH) that was significantly more f requent than expected (P < 0.05) thus interpreted as nonrandom LOH sel ected during tumorigenesis. The overall extent of chromosomes undergoi ng LOH i.e. fractional allelic loss (FAL, the ratio of LOH-positive ma rkers to the total number of informative markers) was measured in each tumor patient. Nonrandom LOH was found on 17p (48.0%), 18q (38.4%), 1 3q (38.1%) and 9p (36.4%). Overall, there were no significant phenotyp es correlated with allelic loss on specific chromosome regions. Based on a bimodal distribution of FAL values with two peaks bordered by a m ean of 0.233, tumors were classified into LOH-related (> 0.233) and LO H-unrelated (< 0.233) types. Among 24 patients with LOH-related tumors , increase in the infiltrative type of growth pattern was found to cor respond with a significant trend of increasing FAL values. This study shows that the growth pattern of gastric carcinoma is correlated with FAL, suggesting that a malignant phenotype is influenced by LOH event.