Abstract
Genetic instability is a hallmark of malignancy, and microsatellite instability is a widely appreciated mechanism of generating genetic changes. We have recently observed four markers clustered on chromosome 20 that showed the effects of microsatellite instability in the gastric adenocarcinoma cell line SNU-1. Each affected marker had alleles of three different sizes. The aim of this study was to investigate the origin for this high-density polymorphism on a single chromosome. The high polymorphism located on chromosome 20 was confirmed using 37 additional markers. To further evaluate this finding, 15 clones of the cell line were generated and then assayed with the triallelic markers. All told, almost a third of the markers on chromosome 20 had triallelic patterns, but only 0.3% of the markers not on chromosome 20 showed this result. The number of clones showing allelic variation was an average of 50% greater for chromosome 20 markers than for markers elsewhere. A karyotype analysis showed that the progenitor cell line of SNU-1 was trisomic for chromosome 20, and the high polymorphism on that chromosome is almost certainly due to the trisomy. Not only are there more chromosome copies and therefore more gene copies subject to mutation in cells containing trisomy, but also more mutations may be passed on to the progeny. This elevated polymorphism increases the repertoire of genetic changes that could affect cellular growth, and may independently increase genomic instability.
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