Genetic instability and Cancer How can a normal cell become a cancer cell? Understanding the basis of cancer is directly linked to the molecular understanding of life and death, a central question in biology. Cancer nowadays is considered as a disease of genetic instability. That is, accumulated mutations in our genes promote unlimited cell growth, escape from death, invasion, and metastasis. To obtain these seemingly impossible properties, thousands of genes must be mutated. However, the calculated normal mutation rate (10-7/gene/generation) never allows a normal cell to become a cancer cell in our lifetime. Thus, initiation of tumorigenesis must accompany mutations in a gene (or genes) that serves a critical role in maintaining genetic integrity. Genes that regulate cell cycle, apoptosis, DNA repair, and chromosome segregation are best candidate genes crucial in the maintenance of genetic fidelity. When these are disrupted, cells then achieve much higher rate mutations (increasing to 105~7 –fold), leading to cancer.