Retinoblastoma

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What is retinoblastoma?

Retinoblastoma is a rare type of eye cancer that develops in the retina, the part of the eye that detects light and color. Although this disorder can occur at any age, it usually develops in young children.

Most cases of retinoblastoma occur in only one eye, but both eyes can be affected. The most common sign of this disorder is a visible whiteness in the normally black pupil (the opening through which light enters the eye). This unusual whiteness is particularly noticeable in photographs taken with a flash, and is called cat's eye reflex or leukocoria. Other signs and symptoms of retinoblastoma include crossed eyes or eyes that do not point in the same direction (strabismus); persistent eye pain, redness, or irritation; and blindness or poor vision in the affected eye.

People with the hereditary form of retinoblastoma may also develop a tumor in the brain called pinealoma. Pinealoma develops in the pineal gland, which is located at the base of the skull. The presence of retinoblastoma and pinealoma together is called trilateral retinoblastoma. Later in life, people with hereditary retinoblastoma also have an increased risk of developing bone cancer (osteosarcoma), soft tissue cancers, a form of skin cancer called melanoma, and other types of cancer.

How common is retinoblastoma?

Retinoblastoma affects an estimated 1 in 15,000 to 20,000 live births. This disease is diagnosed in about 250 children per year in the United States. It accounts for about 3 percent of all cancers in children younger than 15 years.

What are the genetic changes related to retinoblastoma?

Retinoblastoma is a chromosomal condition related to chromosome 13.

Variations of the RB1 gene increase the risk of developing retinoblastoma.

Mutations in the RB1 gene are responsible for most cases of retinoblastoma. RB1 is a tumor suppressor gene, which means it normally keeps cells from growing and dividing too rapidly or in an uncontrolled way. Most mutations in the RB1 gene prevent it from making any functional protein, so it is unable to effectively regulate cell division. As a result, cells divide uncontrollably and form a tumor.

A small percentage of retinoblastoma cases are caused by a deletion in the region of chromosome 13 that contains the RB1 gene. Geneticists refer to this region as 13q14. Children with these chromosomal deletions may also have mental retardation, slow growth, and characteristic facial features (such as prominent eyebrows, a short nose with a broad nasal bridge, and ear abnormalities).

Can retinoblastoma be inherited?

Mutations in the RB1 gene are inherited in an autosomal dominant pattern, which means that one copy of the altered gene in each cell is sufficient to increase cancer risk. A person with retinoblastoma may inherit an altered copy of the gene from one parent, or the altered gene may be the result of a new mutation. For retinoblastoma to develop, a second mutation in the other copy of the RB1 gene must occur in retinal cells during the person's lifetime.

If there is a family history of the disease or if a person develops tumors in both eyes, the RB1 mutation is probably in all of the person's cells, including sperm or egg cells. This person is said to have the inherited form of retinoblastoma, and there is a risk of passing on the mutated RB1 gene to the next generation. However, if only one eye is affected and if there is no family history of the disorder, the RB1 gene may be mutated only in tumor cells. This person likely has the noninherited form of retinoblastoma, and there is no increased risk to other family members.

The small number of retinoblastoma cases caused by chromosome 13 deletions are usually not inherited. These chromosomal changes occur as random events during the formation of reproductive cells (eggs and sperm) or during cell division early in fetal development.

Source: National Institutes of Health

Research on cell biology described by F. De Santa and colleagues

"Here we report that pRb promotes cyclin D3 protein accumulation in differentiating myoblasts by preventing cyclin D3 degradation. We show that cyclin D3 displays rapid turnover in proliferating myoblasts, which is positively regulated through glycogen synthase kinase 3beta (GSK-3beta)-mediated phosphorylation of cyclin D3 on Thr-283. We describe a novel interaction between pRb and cyclin D3 that maps to the C terminus of pRb and to a region of cyclin D3 proximal to the Thr-283 residue and provide evidence that the pRb-cyclin D3 complex formation in terminally differentiated myotubes hinders the access of GSK-3beta to cyclin D3, thus inhibiting Thr-283 phosphorylation. Interestingly, we observed that the ectopic expression of a stabilized cyclin D3 mutant in C2 myoblasts enhances muscle-specific gene expression; conversely, cyclin D3-null embryonic fibroblasts display impaired MyoD-induced myogenic differentiation," wrote Santa F. De and colleagues, .

The researchers concluded: "These results indicate that the pRb-dependent accumulation of cyclin D3 is functionally relevant to the process of skeletal muscle cell differentiation."

De and colleagues published their study in Molecular and Cellular Biology (pRb-dependent cyclin D3 protein stabilization is required for myogenic differentiation. Molecular and Cellular Biology, 2007;27(20):7248-65).

Additional information can be obtained by contacting F. De Santa, CNR-Istituto di Neurobiologia e Medicina Molecolare, Fondazione S Lucia, Via Fosso di Fiorano, 64-00143 Roma, Italy.

The publisher of the journal Molecular and Cellular Biology can be contacted at: American Society Microbiology, 1752 N St. NW, Washington, DC 20036-2904, USA.

Keywords: Italy, Roma, Cell Biology, Cellular.

This article was prepared by Life Science Weekly editors from staff and other reports. Copyright 2007, Life Science Weekly via NewsRx.com.