Study identifies potential gain of function mutation in retinoblastoma

A new research paper was published in Volume 16 of Genes & Cancer on January 20, 2025, entitled, "Analysis of pathogenic variants in retinoblastoma reveals a potential gain of function mutation."

Researchers from Instituto de Física Universidad Autónoma de San Luis Potosí and Hospital Central "Ignacio Morones Prieto" have found a new way a gene mutation might contribute to retinoblastoma, a type of eye cancer that affects young children. The study suggests that a specific genetic change, pR552*, may not only stop the gene from working properly but could also give it a new function that leads to cancer growth. This challenges the common belief that both copies of the retinoblastoma gene (RB1) must be damaged for cancer to develop.

Retinoblastoma is the most common eye cancer in children under five years old. It happens when RB1, which usually helps control cell growth, stops functioning correctly. When this happens, cells can grow uncontrollably and form tumors in the eye. Early signs include the appearance of a white glow in the pupil, misaligned eyes, or vision problems, and prompt detection and treatment can significantly improve outcomes for children.

In this study, the scientists, using in vitro human cell models, examined three specific changes in the RB1 gene. They found that one of them, pR552*, made cells grow, survive, and move more than usual. Unlike other mutations, this one seemed to have an additional harmful effect, even when only one copy of the gene was affected.

The researchers also studied a family in Mexico where the pR552* mutation was passed down from the father to all three of his children, each of whom developed retinoblastoma. This suggests that the mutation might be more powerful than previously thought, possibly causing cancer even if the second copy of the gene is normal.

This discovery could change the way clinicians understand and treat retinoblastoma. Until now, it was believed that both copies of the RB1 gene needed to be damaged for the disease to appear. But this study suggests that just one faulty copy of the gene might be enough to start the disease. If confirmed, these findings could support the development of genetic screening tools to identify at-risk children earlier and inform personalized treatment strategies.

"This mutant pR552* has been identified with high recurrence in different studies in Vietnamese, Portuguese, Canadian, American, English, and Mexican (this work) patients among others; consequently, we decided to continue studying this particular mutant."

The researchers plan to continue studying this mutation to better understand how it works and whether it also plays a role in other cancers, such as bone and brain tumors. Their work could lead to new approaches for fighting retinoblastoma and possibly other cancers linked to the RB1 gene.