Gene Mutations Map Sheds Light on Tumor Growth

Scientists from the University of Edinburgh have produced a detailed map showing how hundreds of possible mutations in a key cancer gene affect tumor growth. The research, published in Nature Genetics, focused on CTNNB1, a gene that encodes the protein β-catenin, which plays an essential role in regulating tissue repair and growth. When this regulation is disrupted, cells may grow uncontrollably, a defining characteristic of cancer.

The study concentrated on a small “hotspot” region in CTNNB1, commonly altered in many types of cancer. Normally, this area acts as a tag that marks β-catenin for destruction once it is no longer needed. Mutations in the hotspot interfere with this process, allowing β-catenin to build up and switch on genes that promote tumor formation. Although more than 70 mutations have been identified in this region, it was previously unclear whether these changes influenced cancer growth in the same way or to different degrees.

To address this question, the Edinburgh team systematically tested every one of the 342 possible single mutations within the hotspot using mouse stem cells. These cells are well suited for precise genome editing and share many biological features with human cells. By applying genome-editing tools and a fluorescent reporter assay, the researchers measured how strongly each mutation activated the β-catenin signalling pathway—the system that controls genes associated with cell growth.

The results revealed a broad range of effects. Some mutations only slightly increased β-catenin activity, while others triggered strong activation of the pathway. When the researchers compared these findings with genetic data from thousands of cancer patients, they found that the experimental scores accurately predicted how β-catenin mutations behave in human cancers. The data also showed that tumors in different tissues tend to select mutations that produce distinct levels of β-catenin activity.

In liver cancer, for instance, two main groups of tumors were identified. Those with weaker CTNNB1 mutations contained more immune cells, while those with stronger mutations had fewer. This pattern suggests that the potency of a mutation may influence how tumors interact with the immune system and how they might respond to immunotherapy.

According to senior author Andrew Wood, “The new map provides a powerful tool for predicting how specific CTNNB1 mutations affect cancer behavior and could support the development of more personalized treatments.”