Other Designations: retinoblastoma 1 (including osteosarcoma); retinoblastoma-associated proteinChromosome: 12Annotation: Chromosome 12, NC_007310.3 (17508776.. 17628174)Gene ID: 534712 RB1Official Symbol RB1 and Name: retinoblastoma 1 (including osteosarcoma) [Gallus gallus] Other Designations: retinoblastoma 1Chromosome: 1Annotation: Chromosome 1, NC_006088.2 (173042817.. 173121034)Gene ID: 386582 Introduction of the GeneDiscussing the gene RB1 itself, we find that the retinoblastoma susceptibility gene, known as RB1, is a tumour suppressor gene located on chromosome 13q. The gene contains instructions for making a protein called pRB with the function of suppressing a tumour i. e. it regulates cell growth and prevents uncontrolled manner. The official symbol for the gene is Rb1 and its other aliases are Rb, Rb-1 and pRb.
pRB can also prevent other proteins from replicating DNA subject to certain conditions. DNA replication refers to a process in which the DNA makes a copy of itself; it occurs before a cell can divide hence regulation of the process can prevent growth of tumours. pRB also influences cell survival and self destruction of cells (apoptosis) by interacting with other proteins. RB1 gene is related to the disease retinoblastoma, many mutations of the gene are found in people infected with the disease.
Somatic mutations, gene mutations in certain cells acquired during the lifetime, are associated with many types of cancers such as bladder cancer, lung cancer and breast cancer as well. The existence of these mutations can also increase the probability of developing other cancers like pinealoma, melanoma and osteosarcoma; making the gene a very interesting subject for an academic discourse. For the development of retinoblastoma, It is necessary that mutations must occur in both copies (alleles) of the gene. According to Barts and The London, “the spectrum of predisposing RB1 gene mutations includes large structural changes (about 10-20%) some of which are also detectable by cytogenetic analysis”.
 Single base substitutions and small insertions/deletions are the other changes. Most of the tumours show a loss of one copy, known as heterozygosity whereas a mutation in the other remaining copy. In almost 10% of tumours we find hypermethylation at the RB1 gene promoter, inhibiting the levels of retinoblastoma protein made by the cell instead of its function. Different types of RB1 mutation can lead to variable penetrance and expressivity, the former refers to the chance of a mutation developing into a cancer and the latter refers t the number of tumours occurring.
Complete penetrance and bilateral retinoblastoma are usually associated with premature termination (truncated protein). The risk of other family members getting the disease depends on whether the victim has a germline RB1 mutation. In non-heritable retinoblastoma we usually have an absence of RB1 mutations in the blood but there is a minute risk of mosaicism. Molecular testing can show which members of a family have a risk of getting retinoblastoma.
The Barts and London Retinoblastoma Genetic Screening Unit performs molecular genetic tests for predisposition to retinoblastoma. They conducted a number of genetic tests, they analyzed over 300 families and the results were compiled. The following table was obtained, RB TypeTestedMutation FoundMutation in BloodSensitivityBilateral & Unilateral with positive family history20619719695.6%Unilateral with no family history1391302593.5%Total345327Overall Sensitivity94.8% However, the genetic tests are not a perfect representation because the techniques used are based on the current knowledge of the RB1 gene. The techniques are not perfectly sensitive and there is a possibility that mutations can be missed in any given sample.
Even when the full mutation screening is negative it may not necessarily mean that the sample is completely free of RB1 mutations. It is even possible when one mutation is detected that there are others which have not been detected.