Nevertheless, rarely VHL can arise without a family history. When both copies of the gene are inactivated by mutation or loss, cell growth is unchecked and tumors result. The two mutation theory of tumor suppression genes originally proposed by Knudson. Each cell contains pairs of chromosomes.
Solid circles are sites of mutations.
Both copies of the gene must be lost for cancer to develop. Chromosomal deletions in lung cancer and renal cancer. Important advances in Oncology. Knudson demonstrated how this model explained why children with hereditary retinoblastomas and Wilms tumors developed multifocal tumors at a younger age, than children with sporadic tumors. The cerebellum, spinal cord, retina, and selected supratentorial sites are susceptible to the development of hemangioblastomas.