Knudson hypothesis

Those of a. Knudson 1971 postulates that tumour development only occurs if both alleles of the (onco-) gene are inactivated. This applies, for example, to autosomal dominant inherited neurofibromatosis type II. Here, tumour development occurs early in the life of the affected person. In sporadic cases (e.g. sporadic formation of schwannomas) only 1 allele is affected due to a congenital germ cell mutation or a somatic de novo mutation ("first hit"). If a further de novo damage ("second hit") of the remaining, normal (wild-type) NF2 allele occurs in the course of life, its function is inactivated (physiological tunor suppressor function). The result is tumor development of the cells, which lose the suppressive function of the remaining, normal (wild-type) NF2 allele.

1. Knudson A (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A 68: 820-823
2. Reeve AE et al (1989) Loss of allelic heterozygosity at a second locus on chromosome 11 in sporadic Wilms' tumor cells. Mol Cell Biol9:1799-1803.
3. Sábado Alvarez C (2008) Molecular biology of retinoblastoma. Clin Transl Oncol 10:389-394.