Figure 1.

Differential expression of the miR transcriptome in the distinctive stages of multistep tumorigenesis. (A) Schematic representation of the separable stages of multistep tumorigenesis in the RT2 transgenic mouse model of PNETs, which afforded the experimental approach to miR transcriptome profiling of discrete stages of carcinogenesis. (B) Clustering analysis of normal, hyperplastic, and angiogenic islet pools, along with pools of primary tumors and of metastases, are shown in the left panel. In the right panel, clustering analysis of 39 individual tumors and six liver metastases reveals that a subset of primary tumors is remarkably similar to metastases in its miR expression profile. Another subset of tumors up-regulates miRs in the Dlk1-Gtl2 imprinted cluster (miRs in red two-thirds of the way down in the left-most primary [purple] tumors as well as in metastases; see also Supplemental Fig. 2).