retinoblastoma

Retinoblastoma is a cancer of the eye that usually appears in early childhood, and it holds a special place in genetics as the disease that revealed how tumor-suppressor genes work. Its story is the reason we understand cancer as something that can need two separate genetic hits before it begins.

The cancer develops in the retina, the light-sensing layer at the back of the eye, when both copies of the RB1 tumor-suppressor gene are lost in a retinal cell. RB1 normally acts as a brake on the cell cycle; without it, immature retinal cells keep dividing and form a tumor. The disease comes in a heritable form, where a child inherits one faulty RB1 copy, and a non-heritable form arising from two acquired hits in a single cell.

Studying which children got retinoblastoma early and in both eyes versus later and in one eye led Alfred Knudson to the two-hit hypothesis, and RB1 became the first cloned tumor-suppressor gene. As an encyclopedic note rather than medical guidance, an early visible sign can be an unusual white reflection in the pupil; in heritable cases the predisposition follows an autosomal dominant pattern in the family.