2-hit hypothesis

Alfred G Knudson; Carl O. Nordling 1953;

The 2-hit hypothesis also Knudson hypothesis explains the recessive inactivation of tumor suppressor genes (Wang LH et al. 2018). It is based on the assumption that tumour formation is the result of several successive mutations in the DNA of the affected cell.

The 2-hit hypothesis also Knudson hypothesis explains the recessive inactivation of tumor suppressor genes (Wang LH et al. 2018). It is based on the assumption that tumour formation is the result of several successive mutations in the DNA of the affected cell.

The first hit means the destruction, loss or inactivation of the first allele either as an inherited or somatically acquired mutation or LOH (Loss of Heterozygosity). In the hereditary forms, the genetic change is detectable in all cells.

The second hit denotes the functional destruction of the still existing and activity-securing second allele by heterozygosity loss or somatic mutation and causes the transformation to a malignant tumor in the Rb gene around retinoblastoma (Mendoza PR et al. 2015). In sporadic cases both hits (Two Hits) are acquired by somatic mutations.

1. Mendoza PR et al (2015) The Biology of Retinoblastoma. Prog Mol Biol Transl Sci 134:503-516.
2. Wang LH et al (2018) Loss of Tumor Suppressor Gene Function in Human Cancer: An Overview. Cell Physiol Biochem. 51:2647-2693.