Correlation of histologic subtypes and replication error phenotype with comparative genomic hybridization in gastric cancer

To characterize phenotypic and genotypic changes in gastric cancer (GC), DN A copy number aberrations (CNAs) were assessed in 53 tumors using comparati ve genomic hybridization (CGH) and correlated with clinicopathologic charac teristics and status of TP53 and replication error (RER). The number of CNA s per tumor was 6.8 (gain 5.3, loss 1.5), and the number of changes was sig nificantly higher in tumors with advanced stage, TP53 mutation, and without RER than in those with early stage (7.7 vs. 3.0), no TP53 mutations (12.4 vs. 4.8) or RER phenotype (8.2 vs. 2.6). Frequent abnormalities included ga ins on chromosomal arms 8q (43%), 6q (26%), 11q(26%), 13q (24%), 7p (23%), 17q (23%), and 20q (23%), and losses on chromosomal arms I bq (26%), 19p (2 3%), 5q (19%), 3p (15%), 4q(15%), and Ip (15%). Advanced GC demonstrated a higher prevalence of gains of 8q (51% vs. 10%, P < 0.05) and loss of 16q (3 3% vs. 0%, P < 0.05) than early GC. Gains on 8q (64% vs. 20%, P < 0.05), 17 q (39% vs. 4%, P < 0.05) and losses on 3p (25% vs. 4%, P = 0.05) and 5q (32 % vs. 4%, 8 < 0.05) were higher in intestinal GC than in diffuse GC. On the other hand, gains on 13q were more common in the diffuse type (40% vs. 11% , 8 < 0.05). As compared with noncardia cancer, cardia cancer showed more g ains on 7p (58% vs. 12%, 8 < 0.05) and 20q (58% vs. 12%, 8 < 0.05) and more losses on 4q (50% vs. 5%, 8 < 0.05). The finding of histology-related aber rations and the combination of CGH and molecular data thus provide addition al evidence suggesting genetic heterogeneity of GC. (C) 2001 Wiley-Liss, In c.