Genetic lineages of colorectal adenocarcinomas with and without adenoma components

We tried to examine whether the de novo colorectal carcinomas (CRCs) without an adenoma component can be discriminated from those deriving from adenoma by DNA copy-number alteration profile. The unsupervised clustering of DNA copy-number profiles of 112 colorectal cancer samples, using large-sized (≥ 9 probes) genes, disclosed 4 clusters: Clusters 1, 3, and 4 correspond to carcinoma with an adenoma component. Cluster 2 and some samples in cluster 3 correspond to carcinoma without adenoma component. Our approach suggested that Cluster 2 may represent de novo CRCs since penetrance plots were very different between cluster 2 and the other clusters. Adenocarcinoma in cluster 3 have higher potential for lymph node metastasis than those in cluster 1 and 4 and can derive from clusters 1/4 tumors. We used formalin-fixed paraffin embedded tissues from 48 colorectal cancers. Genomic DNAs extracted from 112 samples that were taken from adenoma, mucosal, invasive and lymph node parts of tumors were used for array CGH analysis and subsequent hierarchical clustering analysis and penetrance plots