RB1 gene

The RB1 gene (RB1 stands for Retinoblastoma Transcriptional Corepressor 1) is the first classic tumor suppressor gene to be discovered in humans. The gene encodes the retinoblastoma protein (pRb or p105), a nuclear regulatory protein. As a tumor suppressor, pRb ensures that cells do not divide uncontrollably. The RB1 gene is located on chromosome 13, at the 13q14.2 gene locus.

The encoded protein is involved in cell cycle control. pRb inhibits the cell’s transition from the G1 phase to the S phase (DNA replication) by binding to and inhibiting transcription factors (such as E2F). When the cell is ready to grow, pRb is phosphorylated and releases the brake (see also the RB1/E2F regulatory axis).

When it comes to mutations in the RB1 gene, a distinction is made between inherited germline mutations and spontaneously acquired somatic mutations (which occur only in individual tumor cells):

• Mutations in the RB1 gene are primarily associated with retinoblastoma (a malignant retinal tumor that occurs in childhood) as well as an increased risk of other cancers, such as osteosarcoma, bladder cancer, and lung cancer. In the hereditary form, the tumor usually develops very early and often affects both eyes (bilateral).
• Bone and soft tissue tumors (sarcomas): People with a congenital RB1 mutation have a significantly increased lifetime risk of developing secondary tumors, particularly osteosarcomas (bone cancer) and soft tissue sarcomas.
• Small-cell lung cancer (SCLC): Somatic RB1 mutations are very common in aggressive forms of lung cancer, particularly in small-cell lung cancer (SCLC).
• Bladder cancer and breast cancer: A loss of function in the gene is regularly detected in bladder carcinomas as well as in certain forms of breast cancer (e.g., triple-negative breast cancer).
• Other tumor types: Mutations in the RB1 gene also play a role in melanomas, pineoblastomas (often in the context of what is known as a trilateral retinoblastoma), gliomas, and certain types of leukemia.

1. Berry JL et al. (2019) The RB1 Story: Characterization and Cloning of the First Tumor Suppressor Gene. Genes (Basel) 10(11):879.
2. Dimaras H et al. (2015) Retinoblastoma. Nat Rev Dis Primers 1:15021.
3. Indovina P et al. (2019) Translating the predictive value of RB1 into clinical cancer therapy: Are we there yet? Biochem Pharmacol 166:323–334.
4. Knudsen ES et al. (2020) Pan-cancer molecular analysis of the RB tumor suppressor pathway. Commun Biol 3:158.