Randomly occurring mutations of oncogenes and genetic or epigenetic alterations of tumor suppressor genes control many important cellular processes, such as proliferation and apoptosis, involved in human cancer. These genes, as well as those encoding enzymes participating in DNA repair, telomere elongation, inflammation and angiogenesis are the major players during multi-step carcinogenesis. A very important characteristic of oncogenes is that they are active genes that cooperate to induce a transformed phenotype. There are many experimental examples supporting this cooperation, including oncogene transfection studies in cell lines and transgenic mice containing activated oncogenes. These systems and those indicating loss of function in tumor suppressor genes have been models of gene collaboration and multi-step transformation. Alterations disrupting the balance between growth-promoting and growth-inhibiting pathways can lead to cancer, but these alterations can explain only part of the human cancer pathogenesis. The complex mechanisms for regulating apoptosis and the eukaryotic cell cycle are prime targets for oncogenic and tumor suppressor mutations. Only the mutations striking the cancer stem cell population can be transmitted to descendant cells due to their unlimited proliferative potential. It seems that the widespread destabilization of cancer stem cell genomes occurs quite early in multi-step tumor progression. All these findings help molecular oncologists to prevent, diagnose and treat human cancer in more specific ways.
Keywords: Cancer, mutations, oncogenes, genetic alterations, epigenetic alterations, tumor suppressor genes, proliferation, apoptosis, multistep carcinogenesis, transformed phenotype, gene cooperation, transgenic mice, eukaryotic cell cycle, cancer stem cell, tumor progression, molecular oncology.