Angelina Tadros
December 9, 2025
Dr. Barbato
Genetics Blog #7
Mutation Order Shapes Tumour Development Risk
This article is a summary of the research done by Lourenco et al. It investigates how the order of cancer driving mutations affects intestinal tumour development. Using mouse models, the researchers introduced mutations each in different sequences, either priming the intestinal cells first or applying random mutations through ENU (ENU stands for N-ethyl-N-nitrosourea, which is a strong chemical mutagen. It works by adding an ethyl group to DNA bases, which then causes random point mutations in the genome.) before inducing the driver mutations. They found that most cells with early cancer causing mutations were eliminated by the body, but the few that survived made it easier for later mutations to occur. Important genes like APC and β-catenin were more likely to start tumours if the tissue already had earlier priming mutations. Overall this study shows that mutations already present in tissue strongly influence how tumours grow and evolve.
Figure 1.
This graph from the article demonstrates how mice with certain mutations ( such as Apc^het and Kras^G12D) develop more tumours quicker with shorter survival times after ENU treatment, while others (like Arid1a^null and control) have fewer tumours and live longer.
This research shows that cancer doesn't just depend on having driver mutations, but also the order they happen in. Earlier mutations can change the tissue in a way that makes it easier for later mutations to trigger tumour development. The results reflect just how complex tumour development is and it suggests that stopping earlier mutations in some way could help prevent cancer. This study really interested me personally, knowing people whose lives have been affected by cancer, I have always wondered how there is no cure. Science is amazing and has moved so quickly in finding cures for other diseases. This can hopefully provide a major stepping block for more research in better preventative measures in the future.
Article + picture:https://www.nature.com/articles/d41586-025-03748-4
Other similar article: https://medicalxpress.com/news/2025-12-cancer-mutations-affects-chance-tumor.html#google_vignette
Other source: https://pubmed.ncbi.nlm.nih.gov/19614604/#:~:text=Abstract,and%20Dpp10%20(dipeptidylpeptidase%2010).
The mutation order concept is really interesting, it's cool that priming mutations could set the stage for driver mutations to be more effective. It's kind of wild how most early mutations get cleared but the ones that survive actually make the tissue more vulnerable. The personal connection you mentioned definitely makes sense, understanding these sequential steps could actually open up intervention points we didn't know existed before.
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