Genomic instability and DNA ploidy are linked to DNA copy number aberrations of 8p23 and 22q11.23 in gastric cancers

Abstract

The close relationship between chromosomal instability (CIN) and aneuploidy has been reported. The purpose of this study was to identify genomic aberrations present with CIN and aneuploidy in gastric cancers. FISH and image cytometry were applied to 27 sporadic gastric adenocarcinomas to identify CIN-positive tumors and to determine DNA ploidy, respectively. In addition, array-based comparative genomic hybridization was used to identify bacterial artificial chromosome clones that displayed differences in the frequency of copy number aberrations between CIN-positive and CIN-negative tumors, and between aneuploid and diploid tumors. There were many chromosomal regions with DNA copy number aberrations, some of which were nonrandom aberrations linked to the CIN phenotype and aneuploidy. A copy number loss of 22q11.23 was more frequent in CIN-positive cancers than in others (7/12 vs. 2/15, p<0.01) and in aneuploid cancers than in diploid cancers (8/16 vs. 1/11, p<0.05). The frequency of 22q11.23 loss differed significantly between CIN-positive and aneuploid tumors and between CIN-negative and diploid cancers (7/10 vs. 1/9, p<0.01). In contrast, a DNA copy number gain of 8p23.2 was detected in 6 out of 9 CIN-negative/diploid cancers, but was not detected in CIN-positive/aneuploid cancers (p<0.01). There were no cancers carrying both aberrations (22q11.23 loss and 8p23.2 gain). The present study indicates that a 22q11.23 loss and a 8p23.2 gain are markers for both CIN and aneuploidy. This is the first report describing an inverse relationship between the 22q11.23 loss and 8p23.2 gain in terms of genomic instability and DNA ploidy in gastric cancers.