Cancer researchers discover new type of retinoblastoma in babies

INDIANAPOLIS -- (March 15, 2013) -- Not all forms of retinoblastoma, a pediatric cancer of the eye, may be inherited, a discovery that would spare children years of medical evaluations and offer the potential of drug therapy for an aggressive malignancy.

Timothy Corson, Ph.D., a researcher at the Eugene and Marilyn Glick Eye Institute and the Indiana University Melvin and Bren Simon Cancer Center, is a member of an international team that has discovered this childhood eye cancer is not always caused by a mutation of the “retinoblastoma gene.” That’s good news for some children who get this disease because it means they won’t have to undergo invasive exams over the course of their lifetime to determine whether the cancer has spread.

Dr. Corson, who researches pediatric ocular cancers, is one of 25 scientists who have worked on this for several years. Their paper, based on a study of more than 1,000 retinoblastoma patients, was published March 13 in Lancet Oncology. The international team was led by senior author Brenda L. Gallie, M.D., of the Princess Margaret Cancer Centre in Toronto, Canada, and included researchers from the Netherlands, France, New Zealand and Germany.

“Traditionally, an aggressive retinoblastoma seen in a very young infant in the clinic would be suspected to be caused by an inheritable mutation, leading the patient to a childhood full of invasive clinical exams, and the fear of risk to their offspring,” said Dr. Corson, assistant professor of ophthalmology, biochemistry and molecular biology at the Indiana University School of Medicine.

This previously unnoticed class of tumors challenges the long-standing belief that all retinoblastoma are caused by a mutation of the tumor suppressor gene named after this cancer, RB1. Dr. Corson said this new group of retinal tumors has a normal RB1 gene and appears to be “driven” by extra copies of a cancer-causing gene called MYCN, a gene most commonly associated with another childhood cancer, neuroblastoma.

“Our study suggests that one in five patients with an early-onset tumor in a single eye may have MYCN retinoblastoma, and thus lack future risks. This kind of retinoblastoma can only be definitively diagnosed by molecular testing showing lack of mutations in the RB1 gene and amplification of the MYCN gene in the child’s tumor,” Dr. Corson said.

The MYCN retinoblastoma have fewer other mutations in their genome than classic retinoblastoma and have a distinctive cellular appearance to a pathologist, Dr. Corson said. Most importantly, they have features that render them immediately important clinically: They occur at a very young age and are extremely aggressive. In the future, they may be treatable with drugs that block the activity of MYCN.

“This is a landmark discovery in retinoblastoma genetics,” said David A. Plager, M.D., professor of ophthalmology at the Glick Eye Institute and director of the Pediatric and Adult Strabismus Service. “We are currently investigating a patient who fits the clinical description of MYCN retinoblastoma and, if confirmed, it will save the baby and his family the trouble and the expense of numerous future exams to monitor development of a tumor in the other eye.”

Dr. Corson, who immediately began consulting with Dr. Plager on the case, said the child’s definitive diagnosis based on molecular testing could come within weeks.

“This research completely challenges conventional thinking and clinical practice,” senior author Dr. Gallie said. “The common type of retinoblastoma is initiated by loss of a normal gene that can be inherited, so the other eye of the child and infant relatives are at risk to develop tumors. When we remove the eye with a large tumor in very young babies and show it is the new oncogene-driven type of retinoblastoma, there is zero risk for retinoblastoma developing in the other eye or in other infants in the family. This is a major advance in personalized cancer medicine for these children and families.”

About 300 new cases of retinoblastoma arise in the United States annually. Although survival rates are high with treatment, patients are often left with vision loss or blindness.