In this paper Knudson first described his  "two-hit hypothesis," also known as the "Knudson hypothesis," which explains the incidence of hereditary cancers, such as retinoblastoma. 

"Humans inherit two copies of every gene, one from each parent (except for genes on the X and Y chromosomes in males). Some people inherit one mutated version and one normal version of the retinoblastoma gene, which produces the retinoblastoma protein involved in controlling cell cycle progression. The inherited mutation is "the first hit." Over time, a mutation may arise in the normal version in one cell, thus producing "the second hit," which leaves the cell unable to control the process of cell division in an orderly manner, leading to cancer.

"Knudson's insight was to compare the incidence of retinoblastomas, including the number of tumors, the ages of occurrence, and whether tumors occurred in both eyes, among children in families with and without hereditary predisposition to retinoblastomas. Children in families with a hereditary predisposition have more tumors at a younger age and usually have tumors in both eyes. Children in families without the hereditary predisposition usually have only one tumor at a later age.

"The differences in occurrence can be explained by the rate of gene mutation during cell division (a somatic mutation), and a model that requires only one somatic mutation per tumor in hereditary cases but requires two somatic mutations, one on each copy of a particular cell cycle control gene, in one cell lineage in non-hereditary cases, i.e. the co-occurrence of two rare events. Knudson subsequently showed that the model was not only applicable to retinoblastoma but also to Wilms' tumors of the kidney. These studies led to the concept of tumor suppressor genes, which Knudson called "anti-oncogenes." (Wikipedia article on Alfred G. Knudson, accessed 7-22).