Children's Hospital Los Angeles identifies molecular markers to increase precision in treatment of retinoblastoma
In 2017, Jesse Berry, MD, surgeon and ocular oncologist at Children’s Hospital Los Angeles, discovered that fluid removed from the eye during treatment of retinoblastoma contained tumor DNA and functioned as a liquid biopsy—providing information about the tumor and opening the door to earlier diagnosis and treatment.
In her lab’s latest research, published in Nature Communications, the team determined that in addition to diagnosis, aqueous fluid also could be used for prognosis—to ultimately guide treatment decisions that will produce better outcomes for children with more aggressive disease.
Because retinoblastoma occurs at the back of the eye, it is not readily observable. The condition is typically discovered when parents notice a glow in their young child’s eye in low light or after taking a flash photograph. Historically, the child would be presumed to have retinoblastoma, which is a genetic condition, and treated without a definitive diagnosis. The treatment paradigm shifted five years ago when Dr. Berry’s research reported tumor genetic material could be found in the fluid taken from the front of the eye —called the aqueous humor. A confirmed genetic diagnosis became possible before any surgical intervention, allowing for earlier and more defined diagnosis and treatment.
Most retinoblastoma tumors result from a mutation in the Rb gene. But the cancer can also arise from epigenetic changes—genes being switched on to promote tumor growth and disease progression. One of the most significant epigenetic changes—called methylation—is caused by a chemical alteration to the gene that can change a normal cell into a tumor cell. Methylation can turn good, cancer-regulating genes “off” and undesirable, cancer-promoting genes “on.” DNA methylation is a common tumor marker used for diagnosis and prognosis in many other malignancies.
The investigators set out to determine the methylation status in the aqueous humor samples associated with retinoblastoma. They identified a specific methylation signature indicating aggressive tumors and 294 genes that were regulated by methylation to encourage tumor growth.
