Study Offers Valuable Insights Into Mutagenesis Mechanisms and Cancer Evolution

Mutations are the changes in the DNA that gradually occur in human cells as they replicate, and the organism grows and ages. Some of these changes, particularly when they occur in genes, can be instrumental during the development of cancer. Therefore, it is important to differentiate changes that have the potential of being relevant for the disease against others that will accumulate without consequence. The understanding and characterization of the harmless changes is a key methodology used to detect other changes that differ from them and can lead to a better identification of those that are harmful.

In a study published in Nucleic Acids Research, ICREA researcher Dr. Fran Supek and Dr. David Mas Ponte, both at IRB Barcelona, have uncovered variations of mutation rates at a fine scale within genes. Through this study, they have identified "coldspots", where the mutation burden is lower than usual, and have linked them with low DNA methylation, a common epigenetic mark, thereby establishing a direct mechanism linked to their regulation.

Understanding the distribution of mutation rates could facilitate the development of targeted therapies to protect specific genomic regions, or diagnostic tools to monitor these regions. Such therapies could help prevent the accumulation of mutations that drive cancer development or progression."

Dr. Fran Supek, ICREA researcher 

These discoveries stemmed from performing data analysis on mutations found in cancer cells and healthy tissues, together with DNA methylation and other epigenetic datasets.

Mutations and Epigenetics

Epigenetics encompasses chemical modifications on both DNA and the proteins that coat them, such as histones, and regulates gene expression without changing the DNA sequence. DNA methylation is a natural process that can influence how active a gene is, it's one of the most common epigenetic alterations and is particularly important for active genes as they are normally expressed in the tumour. Contrary to other histone modifications, which occur across large sections of the gene, patterns of DNA methylation vary across short segments of the gene and thus are additionally relevant when quantifying the mutation rate variability across the genome and adjacent regulatory regions.

"This study enhances our understanding of factors contributing to uneven mutation distribution within genes, offering valuable insights into mutagenesis mechanisms and cancer evolution," Dr. Supek concludes.

This research project received funding from the European Research Council Consolidator Grant STRUCTOMATIC and the Spanish Ministry of Science and Innovation through a "Plan Nacional" grant and the Severo Ochoa Excellence Programme.

Source:
Journal reference:

Mas-Ponte, D., & Supek, F. (2024). Mutation rate heterogeneity at the sub-gene scale due to local DNA hypomethylation. Nucleic Acids Research. doi.org/10.1093/nar/gkae252.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of AZoLifeSciences.
Post a new comment
Post

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Unlocking the Secrets of Childhood Cancer Genetics