RB1

The RB1 gene provides instructions for making a protein that has several critical functions within cells. The RB1 protein acts as a tumor suppressor, which means that it regulates cell division by keeping cells from growing and dividing too fast or in an uncontrolled way. It is located in the nucleus of cells throughout the body, where it interacts with many other proteins. Under certain conditions, the RB1 protein stops other proteins from triggering the process by which DNA makes a copy of itself (DNA replication). Because DNA replication must occur before a cell can divide, tight regulation of this process controls cell division and helps prevent the growth of cancerous tumors. Additionally, the RB1 protein may play a role in cell survival, controlled cell death (apoptosis), and the process by which cells mature to carry out special functions (differentiation).

retinoblastoma - increased risk from variations of the RB1 gene

More than 400 mutations in the RB1 gene have been identified in people with retinoblastoma, a rare type of eye cancer that typically affects young children. In familial cases of retinoblastoma, a person inherits an altered copy of the RB1 gene from one parent. This mutated gene is present in all of the body's cells. For retinoblastoma to develop, the second copy of the RB1 gene must be mutated or lost in cells of the retina. This second mutation usually occurs early in life. Cells with two inactive copies of this gene produce no functional RB1 protein and are unable to regulate cell division effectively. As a result, retinal cells lacking functional RB1 protein can divide uncontrollably to form a cancerous tumor.

In people with familial retinoblastoma, inherited mutations in the RB1 gene increase the risk of developing several other cancers, usually in adolescence or adulthood. Specifically, people with retinoblastoma are more likely to develop a cancer of the pineal gland in the brain (pinealoma), a type of bone cancer known as osteosarcoma, cancers of soft tissues such as muscle, and a form of skin cancer called melanoma.

In some cases, retinoblastoma occurs in people with no history of the disorder in their family. These cases are described as noninherited or sporadic. Instead of inheriting an altered RB1 gene from a parent, people with sporadic retinoblastoma acquire mutations in both copies of the RB1 gene during their lifetime. These mutations, which are present only in the retina, prevent retinal cells from producing any functional RB1 protein. The loss of this protein allows cells to grow and divide without control or order, leading to the development of a cancerous tumor.

bladder cancer - associated with the RB1 gene

Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. Somatic mutations that inactivate the RB1 gene have been reported in some cases of bladder cancer. Mutations in RB1 are thought to contribute to the development of bladder cancer, and may help predict whether tumors will grow rapidly and spread to other tissues.

other cancers - associated with the RB1 gene

In addition to bladder cancer, noninherited (somatic) mutations in the RB1 gene are associated with many other types of cancer in humans. For example, changes in the RB1 gene have been reported in some cases of lung cancer, a bone cancer known as osteosarcoma, and a form of skin cancer called melanoma. These mutations inactivate the RB1 protein so it can no longer regulate cell division effectively.