2024-07-25 09:15:52
Cancer is caused by genetic changes that occur in our cells over time. There are two main types of mutations: somatic mutations, which are changes in the DNA sequence, and variations in the number of copies of a particular gene. It is known that these two types of mutations interact to promote cancer, but systematic studies explaining the mechanism of action are lacking.
Now, Elizaveta Besedina and Fran Supek, both from the Biomedicine Research Institute of Barcelona (IRB Barcelona), have found that cancer progression is significantly affected by the interaction between changes in copy number and mutations. The study confirms previous research suggesting that a decrease in copy number corresponds to mutations in tumor suppressor genes (blocking their protective functions against cancer), while an increase in copy number corresponds to a greater number of mutations in oncogenes that promote cancer development.
Unexpectedly, researchers have also established a link between an increase in copy number and changes in tumor-reducing genes, and a link between a lower copy number and more changes in many oncogenes. The scientific team noted that both paradoxical associations between mutations and copy number are frequent in cancer genes.
Dr. Besedina and Dr. Supek have provided valuable new insights into the role of genetic mutations in cancer development, opening new ways to consider tumor suppressor genes as potential targets for cancer treatment.
“Our study shows that both increases and decreases in the number of copies can occur in surprising ways, driving the evolution of cancer,” explains Dr. of the University of Copenhagen in Denmark. “This finding challenges the traditional view of how these interactions occur and the idea that we may have missed important events that cause cancer,” he adds.
Second stroke events (or “double hit pattern”): a common feature of cancer
“Double-hit” events involve one type of genetic change, such as a mutation, that occurs in combination with another event, typically a copy number change. This combination increases the effects of individual events and increases the possibility of cancer development.
This relationship is well known in inherited cancer risk variants, such as pathogenic variants in the BRCA1 gene, which cause breast and ovarian cancer. Here researchers focus on unstudied “second hits” involving somatic (ie, non-heritable) mutations. The discovery that these events are common drivers in different types of cancer highlights the importance of considering the combination of different mutations in genomic analyses.
Scientists developed a new method called MutMatch to study the combined effects of mutations and copy number changes on cancer. They analyzed genetic data from 18,000 tumors to discover patterns of genetic changes.
“These two hit events are important for understanding the later stages of tumor progression. “They establish complex relationships between different genetic changes and how they are involved in blood as a whole,” explained Dr. Besedina.
Artistic expression of cancer cells and DNA. (Credit: Amazing Things/NCYT)
Towards a new approach
This study provides a roadmap for future research in cancer genetics. By exploring the relationships between different genetic mutations, scientists can gain a deeper understanding of how cancer develops and progresses. This knowledge could lead to the development of new, more effective treatments for the disease.
Understanding the interplay between mutations and copy number changes allows scientists to identify new targets for cancer treatments, including previously overlooked targets such as tumor suppressor genes. Since these genes have been shown, paradoxically, to also drive cancer through increases in copy number, this suggests that many mutations in them are called “strong negative” mutations. These are, basically, attacked by therapies. This is how this new genetic knowledge can lead to the identification of new anti-cancer drugs or the repurposing of existing ones, which can strengthen their effectiveness.
Finally, knowledge of the different genetic landscapes of tumors may help to divide patients into more precise subgroups, help guide individualized treatment strategies, and identify additional groups of patients. who may benefit from current therapies.
The study is titled “Copy number losses of oncogenes and gains of tumor suppressor genes generate common driver mutations.” And it was published in the academic journal Nature Communications. (Source: IRB Barcelona)
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