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By conducting DNA analysis that examined the type of DNA alteration and its consequences, important insights were gained into the underlying biological processes.

Large-scale DNA analysis forms the basis for improved cancer treatment

Large-scale Dutch DNA analysis provides new insights into the differences between primary and metastatic cancer. The results of this study provide clues to improve and personalize cancer treatment. The findings of this research were published on May 10, 2023, in the scientific journals Nature and Nature Genetics. The extensive data analysis was made possible by the renowned Dutch Hartwig Medical Database.

This research was conducted as part of the Oncode Institute, a collaboration made possible by the Dutch Cancer Society (KWF Kankerbestrijding) and the ministries of Health, Welfare and Sport (VWS), Education, Culture, and Science (OCW), and Economic Affairs (EZ). Researchers from UMC Utrecht, Vall d’Hebron in Barcelona, and the Hartwig Medical Foundation (the founder of the prestigious database of the same name) mapped the DNA alterations of the 23 most common types of tumors. The results of this study can be found in Nature.

Primary and metastatic cancer

Cancer occurs due to DNA alterations that gradually transform a benign cell into a malignant one. This can lead to the spread of cancer to other parts of the body. The study analyzed DNA data from over 7,000 cancer patients. The main research question was: “To what extent are metastatic tumors different from primary cancers?”

In practice, this largely depended on the type of tumor. For some types of tumors, there were no significant differences between the primary tumor and the metastasis, such as in the case of skin cancer. However, for other tumor types, such as lung and prostate cancer, numerous alterations were present, suggesting that the metastatic tumors could be considered as completely different tumors from the originally diagnosed cancer.

DNA analysis sheds light on cancer

By conducting DNA analysis that examined the type of DNA alteration and its consequences, important insights were gained into the underlying biological processes. Research leader Prof. Dr. Edwin Cuppen explains, “The new insights from these studies provide a valuable foundation for improving cancer diagnostics, personalizing therapeutic treatments, and possibly preventing (metastatic) cancer. The study’s outcomes highlight the importance of systematically collecting and unlocking data for reuse in the healthcare domain.”

DNA analysis and escape mechanisms

In the second publication, the researchers delved deeper into the genetic mechanisms that cancer cells employ to evade the immune system. Due to the DNA alterations caused by the tumor, each cancer cell becomes somewhat foreign to the body. Typically, this signals our immune system to recognize and eliminate tumor cells at an early stage. Therefore, a fully developed tumor must have acquired properties to escape this mechanism.

Evading the immune system appears to be a characteristic acquired early in tumor development. Interestingly, certain types of cancer have only one or a few escape strategies, while other types develop a wide variety in this area. These insights from sophisticated DNA analysis using a state-of-the-art Dutch database, as Cuppen explicitly mentioned, provide clues for more targeted treatment, particularly because a properly functioning immune system is essential for the promising effects of immunotherapy in cancer treatment. The results may also serve as a basis for improving therapy choices and preventing overtreatment.

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