Graphic summary. Credit: The American Journal of Human Genetics (2025). DOI: 10.1016 / J.AJHG.2025.01.012
Research led by Qimr Berghofer has shown that new advanced calculation prediction tools can improve the accuracy of genetic tests for families affected by a hereditary condition which considerably increases their risk of cancer development, paving the way for better targeted care.
The results were published in the American Journal of Human Genetics In addition to the complementary studies of international collaborators, which together show how the incorporation of new computer biology tools with existing modeling methods has improved the predictive power of genetic test results.
Calculation tools are used to predict if and how a genetic variant is likely to have an impact on the function of the protein coded by the gene.
Genetic tests are recommended for people suspected of having a fault in a gene, to provide a genetic diagnosis and determine the most appropriate clinical management, such as regular screening, preventive measures and targeted treatments.
However, all genetic variants will not cause harm. The determination of which is benign and which are likely to cause a disease is complex. The rapid progress of genetic sequencing has also led to growing numbers of discovered genetic variants which have not yet been classified.
Professor Amanda Spurdle directs an internationally recognized team at Qimr Berghofer who develops and improves methods to fill this gap in knowledge, better understand what genetic variants are (pathogenic) disease and which are benign.
An area of interest is Li Frameni syndrome, a rare but devastating condition that occurs when people have a fault in the TP53 gene. This gene is known as the “guardian of the genome” because of his key role in deleting tumors. A fault in the way this gene works can increase the risk of developing several cancers at the age of 60 to 95%.
The study by Qimr Berghofer in collaboration with the Health Research Institute of the Hospital Clinico San Carlos in Spain, and the Ambry Genetics clinical genomic test company in the United States, aimed at reducing the number of variants of TP53 genes with an unclear impact using new computer methods to predict variants that have an impact on function.
These included several tools formed to predict the possible structural changes of proteins that could result from a genetic variant and their effect on protein stability. Researchers have shown that the use of these types of tools in combination with existing prediction methods could improve the accuracy of the classification of variants, providing lighter responses to people undergoing tests. This could make the difference between an individual who has access to intensive or not screening.
The study of the Nitsan Rotenberg study of Qimr Berghofer said that this would ultimately support more enlightened clinical decision -making and better patient care.
“Li-Fraumeni syndrome is rare, but for people affected, it is extremely important to give them certainty. We want to reduce the concern that has just discovered that they have a variant in the TP53 gene, but no one knows whether it is pathogenic or not.
“Improving the classification of genetic variants means that those with a pathogenic variant can receive targeted screening that increases the chances of early diagnostic and more effective treatment,” said Rotenberg.
The main author, Professor Amanda SPURDLE, said that the studies of Qimr Berghofer and their international collaborators can help to clarify international guidelines and clinical practice.
“The use of new IT biology tools focused on the forecasting of the protein structure represents a paradigm change in genetic research, offering the potential to transform genomic research and its clinical application.
“We hope to continue to use these tools to improve the accuracy of our assessment of newly discovered and poorly understood genetic variants in hereditary cancer and other areas,” said Professor SPURDLE.
The latter research adds to another important study by the Molecular Cancer Epidemiology group of Qimr Berghofer, published in the journal Human genomic.
This work, led by Dr. Cristina Fortano, has revealed another way in which changes in the TP53 gene can potentially lead to abnormal protein production, by disturbing the crucial “splicing” process, where genetic instructions to form tumor suppression proteins are changed together.
Dr Fortano said: “Together, these studies have significant implications for prediction and personalized cancer risk prevention strategies. The results highlight the rapid evolution of genetic knowledge and the critical need for a regular re -evaluation of the results of genetic tests.”
More information:
Nitsan Rotenberg et al, the integration of protein stability scores and alphamissen improves the prediction of bioinformatics impact for the variants of deletion of false sense amino and within the framework, The American Journal of Human Genetics (2025). DOI: 10.1016 / J.AJHG.2025.01.012
Cristina Fortano et al, exploring the role of splicing in the pathogenicity of variants of TP53 by the predictions and minigen tests, Human genomic (2025). DOI: 10.1186 / S40246-024-00714-5
Supplied by Qimr Berghofer
Quote: IT analysis clarifies the risk of cancer for families with genetic variants (2025, April 29) recovered on April 29, 2025 from
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