Dogs and Tumors: A New Mutation in Gastrointestinal Tumors

Gastrointestinal stromal tumors, or GISTs, are a type of tumor that can grow in the digestive system. These tumors can occur in both dogs and humans. They are often linked to changes, or mutations, in a gene called KIT. Scientists took samples from 55 cases of canine GISTs. They looked for specific changes in three parts of the KIT gene: exons 8, 9, and 11. They found two new mutations in exon 8: A434T and F436S. The A434T mutation did not seem to change how the KIT gene worked. However, the F436S mutation was interesting. It kept the ability to form dimers, which are pairs of molecules that work together. But it lost the ability to phosphorylate, a process where a phosphate group is added to a molecule, which is crucial for many cellular functions. This loss of phosphorylation affected how cells heal wounds and move around. The mutation did not change where the KIT protein was located in the cell. But computer simulations showed that F436S might change the structure of the KIT protein near the cell membrane. This change could affect other parts of the protein, both inside and outside the cell. The F436S mutation is a point mutation, which means it changes just one part of the gene. But this small change can have big effects. For example, when F436S is combined with another known mutation that affects phosphorylation, it reduces the protein's ability to phosphorylate even more. Understanding these mutations can help scientists learn more about how GISTs grow and spread. This knowledge could lead to new treatments for both dogs and humans with these tumors.