Cancer arises through a series of somatic alterations in DNA that result in unrestrained cellular proliferation. Most of these alterations involve actual sequence changes in DNA (., mutations). They may arise as a consequence of random replication errors, exposure to carcinogens (., radiation), or faulty DNA repair processes. While most cancers arise sporadically, familial clustering of cancers occurs in certain families that carry a germline mutation in a cancer gene. Historical Perspective The idea that cancer progression is driven by sequential somatic mutations in specific genes has only gained general acceptance in the past 25 years. .
