A precise method for detecting harmful mutations in tumors has been developed.

Researchers at Sechenov University of the Ministry of Health of Russia have developed a novel approach to tumor genome analysis aimed at precise diagnosis and personalized therapy selection. This bioinformatics method will enhance the identification of harmful mutations, which is crucial for selecting the most effective treatments to combat tumors.

2025-02-19 10:00:14https://naked-science.ru/article/column/mutatsij-v-opuholyah

The results of the study have been published in the scientific journal Cancers. Chimeric transcripts are RNA molecules composed of exons (the segments that provide information used for protein synthesis) from two or more genes. They influence tumor growth and are often targeted in therapies.

Several different methods are employed to study known chimeric transcripts and to discover new ones; however, each method has its drawbacks: low sensitivity, an inability to distinguish mutations that genuinely affect tumor growth from those that occur incidentally and have no functional significance, among others.

Researchers from the Personalized Oncology Institute at the National Center for Medical Research "Digital BioDesign and Personalized Healthcare," established at Sechenov University, have developed a new bioinformatics approach that accurately identifies clinically significant mutations resulting from the fusion of the ALK gene with other genes based on transcriptome sequencing results. Mutations in the ALK gene are associated with a high risk of developing anaplastic large cell lymphoma, neuroblastoma, non-small cell lung cancer, renal cell carcinoma, and squamous cell carcinoma of the esophagus. This method is based on the analysis of exon coverage — that is, how frequently RNA molecules for them are present in the sample.

The scientists analyzed RNA sequencing data from 906 human cancer samples. They employed two NGS panels used in clinical practice to detect chimeric transcripts as controls. The new method allowed for the identification of chimeric transcripts with an accuracy of up to 96 percent — higher than traditional analysis methods. Furthermore, it was able to accurately predict the effectiveness of therapy in patients from whom the samples were taken.

“Today, immunohistochemistry is considered the ‘gold standard’ for identifying chimeric oncogenes, but practice shows that it often yields inaccurate results. As a result, patients may receive treatment that turns out to be ineffective for them. For another analysis method, FISH, it is necessary to know in advance which gene fusion we are searching for. ALK has known 'partners,' but it can also fuse with other genes, and then that chimeric oncogene will be missed. Our analysis accurately indicates whether there is a chimeric oncogene and which one it is,” said Anton Buzdin, the lead researcher at the Personalized Oncology Institute and Doctor of Biological Sciences.

The new test will become part of a platform for identifying oncogenes, which specialists from the Personalized Oncology Institute are developing in collaboration with Oncobox. The test system for molecular diagnostics of tumors promises to be a more precise and less expensive alternative to existing methods for detecting clinically significant mutations in tumors, which will help tailor the most effective treatment regimens.