<prompt> Knudson two hit hypothesis is seen withMelanomaRetinoblastomaUlcerative colitisCrohn disease  <response>: Ref Robbins 9e p290 The Knudson hypothesis, also known as the two-hit hypothesis is the hypothesis that most genes require two mutations to cause a phenotypic change. It was first formulated by Alfred G. Knudson retinoblastoma, a tumor of the retina that occurs both as an inherited disease and sporadically. He noted that inherited retinoblastoma occurs at a younger age than the sporadic disease. In addition, the children with inherited retinoblastoma often developed the tumor in both eyes, suggesting an underlying predisposition. Knudson suggested that two hits to DNA were necessary to cause the cancer. In the children with inherited retinoblastoma, the first mutation in what later came to be identified as the RB1 gene, was inherited, the second one acquired. In non-inherited retinoblastoma, instead two mutations, or hits, had to take place before a tumor could develop, explaining the later onset. 