Two categories of genes namely, proto-oncogenes and tumor suppressor genes in the normal cells undergo mutations prior to malignant Transformation. Proto-oncogenes become oncogenic, whereas tumor suppressor genes are silenced to allow the mutational events in genome to accumulate. The malignant transformation involves initiation, promotion, dis-differentiation, differentiation, proliferation, progression and invasion. At every level of the transformation cascade, gene signatures are found. The cumulative increases of abnormal gene segments manifest in complete cancer phenotypic expression involving both gains and losses of metabolic functions and enables the disease progression to the fatal end in the continuum. Therapeutic intervention may be required at every level of these cascades. Such interventions may prevent initiation and promotion of malignant transformation and oncogenic differentiation at all levels. Studying the gene signatures at every level of malignant transformation is critical for personalized therapy for controlling lymph node and/or organ metastasis, as well as to improve both overall and disease-free survival of the cancer patients.
