Tracking cancer dynamics from normal tissue to malignancy using perfect N- and T-gene expression markers

Common knowledge states that the spontaneous somatic evolution of a normal tissue may lead to a tumor. Once the tumor is formed, it naturally evolves towards a state of higher malignancy. On the other hand, perfect gene expression markers for normal tissue and tumor--the so-called N-genes and T-genes--were recently introduced. We join these two pieces of knowledge in order to argue that: 1) Only N-markers participate in the spontaneous dynamics of a normal tissue. The number of active markers decreases as the tissue approaches the transition point where it becomes a tumor. 2) Only T-markers participate in the spontaneous dynamics of tumors. The number of markers increases as the tumor becomes more malignant. 3) Both sets of genes are connected by the so-called NT-genes, i.e., genes that are simultaneously N- and T-markers. They should play a crucial role at the transition point and, possibly, when the tumor is exposed to a drug or therapy. 4) The pathways or mechanisms protecting the normal tissue from becoming a tumor may be described by a small perfect panel of N-genes. 5) The pathways or mechanisms guiding the evolution of tumors in a tissue may be described by a small perfect panel of T-genes. We illustrate the above statements with the analysis of expression data for prostate adenocarcinoma, one of the most heterogeneous tumors. In this case, there are about 1000 N-genes and 6000 T-genes, and the perfect N- and T-panels contain 11 and 8 genes, respectively. Additionally, we provide examples from lung adenocarcinoma and liver hepatocarcinoma.