The retinoblastoma (RB) tumor-suppressor gene is cloned

Historical milestone — this page describes an event dated 1986. It is not current breaking news.

The paper

In 1986, Stephen Friend and colleagues published "A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma" in Nature, volume 323, pages 643 to 646.

They had isolated the RB gene. It was the first tumor suppressor gene ever cloned, and it changed how researchers thought about what causes cancer.

The cancer at the center of it

Retinoblastoma is a cancer of the retina, the light-sensing layer at the back of the eye. It is a disease of very young children.

NCI reports that it makes up about 3% of cancers in children under 15, and that two-thirds of cases are diagnosed before age 2. The estimated incidence is roughly 3 cases per million children under 20 each year. In children aged 0 to 4, where the disease is concentrated, that rises to 18.4 per million.

Some children have a tumor in one eye. Others have tumors in both. Which of those happens is not random, and working out why led directly to this gene. Our retinoblastoma page covers the disease itself in more depth.

Two kinds of cancer gene

By the 1980s researchers knew about oncogenes: genes that, when damaged, actively push a cell to divide. One faulty copy is enough. The damage acts like a stuck accelerator.

The 1986 paper's abstract sets out the other possibility. Some cancer-predisposing mutations are recessive — they only matter when both copies are lost. That is a failed brake rather than a stuck accelerator, and retinoblastoma was the model case for it.

The split still shapes cancer genetics. Oncogenes are gained; tumor suppressors are lost. A drug can block an overactive protein fairly readily. Restoring a missing one is much harder. That is why the two groups have led to very different treatments.

How they found it

The gene sits on the long arm of chromosome 13, at a spot labeled 13q14. Researchers had narrowed it to that band because the region was repeatedly missing in tumor cells.

The team isolated a stretch of DNA there of roughly 70,000 letters. Then came the test that made the case. The segment was active in many other tumor types, but produced no detectable RNA in retinoblastomas or osteosarcomas — bone tumors that these children develop at raised rates. A gene switched off exactly where the cancer appears, and switched on elsewhere, is the behavior a brake gene should show.

The abstract also notes that mutations at this spot may be inherited from a parent, may arise as egg and sperm cells form, or may occur in ordinary body cells during life.

Why families were affected first

Before this, an inherited risk of retinoblastoma could only be inferred from family history and from how many eyes were involved. After it, the actual change could eventually be tested for.

That matters in practice. NCI notes that children who inherit a mutation carry a high risk of second tumors outside the eye later on. That risk changes how they are followed for decades. Knowing a child's status also tells a family whether siblings and future children need eye exams. Our page on genetic testing for cancer risk covers how such testing is offered now.

How retinoblastoma is found and treated today

The diagnosis is unusual in oncology: it is normally made without a biopsy. Taking tissue from inside the eye risks spreading the tumor.

Instead, NCI describes an exam under anesthesia. The pupil is fully dilated and the eye wall gently indented, so the whole retina can be seen. The team records the number, position, and size of tumors. They also note any retinal detachment, and any seeding into the fluid of the eye. Ocular ultrasound and MRI help rule out other causes and show whether disease has reached beyond the eye. CT scans are usually avoided in these children because of radiation.

Treatment has two goals at once, and NCI states them plainly: save the child's life, and keep useful vision where possible. For disease that has spread outside the eye, chemotherapy given through the bloodstream plus radiation is likely to cure it. Disease past the eye socket needs stronger chemotherapy. That can include high doses, followed by a rescue using the child's own blood stem cells.

Warning signs in a young child

Two signs account for most presentations, and both are visible rather than felt:

• A white pupil reflex. Instead of the usual red-eye in a flash photograph, one pupil looks white or cloudy. NCI notes this is often first spotted in a photo. It needs an eye examination, not a wait-and-see.
• A turned eye. One eye drifting inward or outward is the second most common presenting sign.

Later signs of an advanced tumor include eye pain, redness and swelling around the eye, an enlarged eyeball, and vision that is clearly poor on one side. Any of these in a child under 5 warrants a same-week appointment with a clinician who can dilate the pupil. Our childhood cancer overview explains how these cancers differ from adult ones.

What this finding cannot tell you

• Isolating the gene did not produce a treatment. There is still no drug that restores a lost tumor suppressor, and retinoblastoma is treated with chemotherapy, local therapies, radiation, and surgery.
• RB turned out to be altered in many cancers beyond the eye and bone tumors it was found in, so its role is broader than the 1986 paper could describe.
• A single gene rarely explains an adult cancer. Most involve many changes accumulated over years.
• This page summarizes a historical event. It is not medical advice about anyone's care, and it is not a guide to whether a specific child should be tested.

Sources

This article was written from the sources below, which were checked on the source-check date shown above.

• Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP, "A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma," Nature 1986;323(6089):643-6 (PMID 2877398): https://pubmed.ncbi.nlm.nih.gov/2877398/
• National Cancer Institute, Retinoblastoma Treatment (PDQ), health professional version: https://www.cancer.gov/types/retinoblastoma/hp/retinoblastoma-treatment-pdq
• National Cancer Institute, Childhood Cancers: https://www.cancer.gov/types/childhood-cancers

How this page was made

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. It is not a diagnostic service, does not recommend treatments, and is not for emergencies.

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