Abstract
Retinoblastoma (Rb) is the most common intraocular malignant tumour in childhood, with an incidence of 1 in 15,000 live births. Complete information on this rare tumour can be easily accessed through the internet, although many aspect concerning the aetiology and pathogenesis of the disease, are still controversial. The βtwo hitβ theory, formulated in 1971 to explain the variegated clinical expression of the disease, is based on the idea that single gene mutation may determine the development of cancer. However, this view does not take into account the most recent evidences showing the role of aneuploidy and chromosome instability in cancer. Also, a number of other genes and epigenetic mechanisms are involved in the genesis of retinoblastoma. More importantly, the βtwo hitβ theory makes predictions, concerning the age distribution of the tumour, its mode of βtransmissionβ (hereditary retinoblastoma), and its pathogenesis, which are not fulfilled by the clinical reality. Overall, the βtwo hitβ theory represents a rather simplistic and outdated model to explain tumour development and clinical evolution of retinoblastoma. Β© 2007 WileyβLiss, Inc.