RESEARCH STARTER

RB1 gene and cancer

The RB1 gene, located on chromosome 13, is a critical tumor-suppressor gene that plays a vital role in regulating cell division. Its primary function is to produce the retinoblastoma protein (pRB), which controls the cell cycle by interacting with transcription factors and silencing specific genes. Inactivation of the RB1 gene can lead to retinoblastoma, a rare form of childhood cancer that typically manifests in children from in utero to around five years of age. There are two forms of retinoblastoma: hereditary, where one defective RB1 gene is inherited and the second copy is mutated during development, and sporadic, where both copies of the gene are mutated in the same somatic cell.

Retinoblastoma accounts for approximately 2-3% of cancers in children, with an incidence rate of about 1 in 14,000 to 1 in 20,000. Children with inherited RB1 mutations face an increased risk of developing other cancers later in life, such as those affecting the bladder, pineal gland, and skin. Molecular screening methods can help identify RB1 mutations, potentially reducing the need for invasive clinical screening. Understanding the RB1 gene's role in cancer helps in early detection and intervention strategies, which can significantly impact outcomes for affected individuals.

Full Article

  • ALSO KNOWN AS: Retinoblastoma 1 (including osteosarcoma), OSRC

DEFINITION: The RB1 gene (a tumor-suppressor gene), which is 180 kilobase pairs with 27 exons, can become inactivated and cause retinoblastoma, a rare childhood cancer of the retina, occurring from in utero to about five years of age.

Gene location and function: The retinoblastoma gene, RB1, is on chromosome 13q14.2. This ubiquitously expressed gene codes for a 110 KDa tumor suppressor (pRB), which regulates cell division. The retinoblastoma protein regulates the progression of cells through the cell cycle and the exiting of differentiating cells from the cell cycle. This protein controls the cell cycle by sequestering transcription factors and by deacetylating histones, which are involved in gene silencing. Both copies of the RB1 gene must be mutated to lose the tumor-suppressor ability. Individuals with an inherited form of retinoblastoma have a germline mutation of one RB1 gene. During development, the second copy of the RB1 gene is mutated; control of the cell cycle is lost, and tumors develop. These tumors may be in both eyes. Other individuals have sporadic retinoblastoma, in which mutations occur in the same somatic cell to inactivate both copies of the RB1 gene. Sporadic retinoblastoma is often in only one eye.

RB1 gene inactivation: Causes of RB1 gene inactivation include chromosome rearrangements of the 13q14 region, nucleotide changes, loss of heterozygosity (loss of the normal copy), and CpG hypermethylation in the RB1 promoter region (which silences the gene).

Molecular screening: Methods to screen for RB1 gene mutations include multiplex polymerase chain reaction (PCR) sequencing of the gene, a protein truncation test, and methylation analysis. The usual clinical screening for retinoblastoma requires examination of the eyes under anesthesia. Molecular screening could eliminate anesthesia-related risks and reduce the financial and psychological costs of clinical screening. Individuals without germline RB1 mutations will not need the clinical screening. Fetuses with highly penetrant germline mutations could be delivered early and treated sooner to save their vision. People with inherited forms of retinoblastoma (having one defective RB1 gene) have an increased risk of developing other cancers, such as those of the bladder, pineal gland, bone, and skin.

Incidence: Retinoblastoma accounts for roughly 3 percent of childhood cancers. Roughly 300 to 350 cases are diagnosed annually throughout the United States. According to a study published in 2021 in the British Journal of Cancer, patients with hereditary retinoblastoma had a higher risk of developing other cancers, including sarcomas and melanoma, later in life. RB1 mutations also appeared to play a role in hastening the spread of advanced lung cancer to the bones.



Bibliography

“Key Statistics for Retinoblastoma.” American Cancer Society, 11 Sept. 2025, www.cancer.org/cancer/types/retinoblastoma/about/key-statistics.html. Accessed 19 Nov. 2025.

Lohman, Dietmarr. “Retinoblastoma - GeneReviews®.” NCBI, 21 Sept. 2023, www.ncbi.nlm.nih.gov/books/NBK1452. Accessed 19 Nov. 2025.

“Retinoblastoma.” Texas Children's Hospital, www.texaschildrens.org/content/conditions/retinoblastoma. Accessed 19 Nov. 2025.

Zelley, Kristin. “Retinoblastoma (Eye Cancer in Children).” Children's Hospital of Philadelphia, www.chop.edu/conditions-diseases/retinoblastoma. Accessed 19 Nov. 2025.

Zhou, et al., Chenghzi. “RB1 Mutation Had an Influence on Bone Metastases in Advanced Treatment-naïve Lung Cancer.” Journal of Clinical Oncology, vol. 38, no. 15, 2020. ASCO Publications, ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.e21668. Accessed 19 Nov. 2025.

Full Article

  • ALSO KNOWN AS: Retinoblastoma 1 (including osteosarcoma), OSRC

DEFINITION: The RB1 gene (a tumor-suppressor gene), which is 180 kilobase pairs with 27 exons, can become inactivated and cause retinoblastoma, a rare childhood cancer of the retina, occurring from in utero to about five years of age.

Gene location and function: The retinoblastoma gene, RB1, is on chromosome 13q14.2. This ubiquitously expressed gene codes for a 110 KDa tumor suppressor (pRB), which regulates cell division. The retinoblastoma protein regulates the progression of cells through the cell cycle and the exiting of differentiating cells from the cell cycle. This protein controls the cell cycle by sequestering transcription factors and by deacetylating histones, which are involved in gene silencing. Both copies of the RB1 gene must be mutated to lose the tumor-suppressor ability. Individuals with an inherited form of retinoblastoma have a germline mutation of one RB1 gene. During development, the second copy of the RB1 gene is mutated; control of the cell cycle is lost, and tumors develop. These tumors may be in both eyes. Other individuals have sporadic retinoblastoma, in which mutations occur in the same somatic cell to inactivate both copies of the RB1 gene. Sporadic retinoblastoma is often in only one eye.

RB1 gene inactivation: Causes of RB1 gene inactivation include chromosome rearrangements of the 13q14 region, nucleotide changes, loss of heterozygosity (loss of the normal copy), and CpG hypermethylation in the RB1 promoter region (which silences the gene).

Molecular screening: Methods to screen for RB1 gene mutations include multiplex polymerase chain reaction (PCR) sequencing of the gene, a protein truncation test, and methylation analysis. The usual clinical screening for retinoblastoma requires examination of the eyes under anesthesia. Molecular screening could eliminate anesthesia-related risks and reduce the financial and psychological costs of clinical screening. Individuals without germline RB1 mutations will not need the clinical screening. Fetuses with highly penetrant germline mutations could be delivered early and treated sooner to save their vision. People with inherited forms of retinoblastoma (having one defective RB1 gene) have an increased risk of developing other cancers, such as those of the bladder, pineal gland, bone, and skin.

Incidence: Retinoblastoma accounts for roughly 3 percent of childhood cancers. Roughly 300 to 350 cases are diagnosed annually throughout the United States. According to a study published in 2021 in the British Journal of Cancer, patients with hereditary retinoblastoma had a higher risk of developing other cancers, including sarcomas and melanoma, later in life. RB1 mutations also appeared to play a role in hastening the spread of advanced lung cancer to the bones.



Bibliography

“Key Statistics for Retinoblastoma.” American Cancer Society, 11 Sept. 2025, www.cancer.org/cancer/types/retinoblastoma/about/key-statistics.html. Accessed 19 Nov. 2025.

Lohman, Dietmarr. “Retinoblastoma - GeneReviews®.” NCBI, 21 Sept. 2023, www.ncbi.nlm.nih.gov/books/NBK1452. Accessed 19 Nov. 2025.

“Retinoblastoma.” Texas Children's Hospital, www.texaschildrens.org/content/conditions/retinoblastoma. Accessed 19 Nov. 2025.

Zelley, Kristin. “Retinoblastoma (Eye Cancer in Children).” Children's Hospital of Philadelphia, www.chop.edu/conditions-diseases/retinoblastoma. Accessed 19 Nov. 2025.

Zhou, et al., Chenghzi. “RB1 Mutation Had an Influence on Bone Metastases in Advanced Treatment-naïve Lung Cancer.” Journal of Clinical Oncology, vol. 38, no. 15, 2020. ASCO Publications, ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.e21668. Accessed 19 Nov. 2025.

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