RB1

The RB1 gene, also known as the retinoblastoma 1 gene, is a crucial tumor suppressor gene located on chromosome 13q14.2. It encodes the retinoblastoma protein (pRb), which plays a pivotal role in regulating the cell cycle, particularly the transition from the G1 phase to the S phase. Mutations in the RB1 gene are associated with the development of retinoblastoma, a rare form of eye cancer that primarily affects young children, as well as other cancers.

Function

The RB1 gene product, pRb, is a key regulator of the cell cycle. It functions by inhibiting the activity of E2F transcription factors, which are necessary for the progression of the cell cycle from the G1 phase to the S phase. In its hypophosphorylated state, pRb binds to E2F, preventing the transcription of genes required for DNA replication. When pRb is phosphorylated by cyclin-dependent kinases (CDKs), it releases E2F, allowing the cell cycle to proceed.

Role in Cancer

Mutations in the RB1 gene can lead to the loss of pRb function, resulting in uncontrolled cell proliferation. This loss of function is a hallmark of retinoblastoma, a pediatric cancer of the retina. In addition to retinoblastoma, RB1 mutations are implicated in other cancers, such as osteosarcoma, small cell lung cancer, and breast cancer. The RB1 gene is often inactivated in these cancers through deletions, point mutations, or promoter hypermethylation.

Genetic Testing and Diagnosis

Genetic testing for RB1 mutations is crucial for the early diagnosis and management of retinoblastoma. Families with a history of retinoblastoma may benefit from genetic counseling and testing to assess the risk of developing the disease. Early detection allows for timely intervention, which can improve outcomes and preserve vision.

Therapeutic Implications

Understanding the role of RB1 in cancer has led to the development of targeted therapies aimed at restoring pRb function or compensating for its loss. Research is ongoing to develop drugs that can inhibit CDKs, thereby preventing the phosphorylation and inactivation of pRb. Such therapies hold promise for treating cancers with RB1 mutations.

Also see

• Retinoblastoma
• Tumor suppressor gene
• Cell cycle
• E2F transcription factor
• Cyclin-dependent kinase