Progression risk of gland-forming gastric neoplasms assessed by DNA copy-number profiling

We tried progression risk prediction of individual gland-forming gastric cancers using genomic DNA copy number profile as a genetic lineage marker. The unsupervised clustering of DNA copy-number profiles of 107 gastric cancer samples, using large-sized (≥ 6 probes) genes, were divided into the loss-rich (A) and gain-rich (B) clusters. The T1/T2-4 ratio was significantly higher in cluster B and in cluster A (P < 0.0007). Small cancers (≤ 2 cm in diameter) were more frequent in cluster B than in cluster A. These 2 clusters were not linked to the frequency of metastasis but to the liability to progression from early to advanced stage; the cluster A may more readily become advanced than cluster B. Our approach suggested that the genetic lineages of early and advanced gland-forming gastric cancers are largely different; the eradication of small cluster B tumors (≤ 2 cm) by the present ESD indication may be valid, but not be effective for reduction of large, aggressive cluster A tumors. We used formalin-fixed paraffin embedded tissues from 55 gland-forming invasive gastric cancers with or without LN metastasis. Genomic DNAs extracted from 107 samples that were taken from mucosal, invasive and lymph node parts of tumors were used for array CGH analysis and subsequent hierarchical clustering analysis and penetrance plots