Researchers from the Department of Pathology at Amsterdam UMC have solved a persistent problem in lung cancer care. Thanks to genetic analysis of a tumor’s DNA, doctors can now determine with certainty whether multiple tumors in a patient’s lung are separate primary tumors or metastases originating from a single tumor. This distinction is essential, as it determines whether treatment is aimed at cure or at symptom control.
Why traditional methods were not decisive
Until recently, doctors could not reliably make this distinction using imaging and microscopic examination alone. Tumors may look very similar under the microscope even when they arise independently. At the same time, metastases can sometimes appear different from the original tumor. This uncertainty often led to difficult and potentially risky treatment decisions.
“The lung is an organ to which tumors from many other organs can spread. In daily practice, this creates an important dilemma for pathologists: is it a metastasis from another tumor, or a primary lung tumor? Our research shows that existing DNA tests, which are widely available in many pathology laboratories, can be used much more precisely to resolve this problem” - researcher Teodora Radonic
DNA analysis provides clear answers
The research team—Jurriaan Janssen, Yongsoo Kim, Teodora Radonic, and Bauke Ylstra—has shown that with advanced DNA tests, it is possible to determine very precisely whether tumors in a patient are related or not. They used advanced DNA-tests and analyzed large datasets from hundreds of patients in the Netherlands, Germany, Portugal, and the United Kingdom to validate these tests. This approach revealed far more detail than routine diagnostic methods.
From small panels to whole-genome analysis
Small DNA test, currently used in routine care, can distinguish tumors for approximately 50–75% of patients. Larger panels increase accuracy to nearly 98%,while Whole-genome analysis, examining all 25,000 genes, allows correct classification for 100% of these patients. Although this latter approach is still too complex for daily clinical use, it serves as the gold standard to validate all other tests.
A new test for the most complex cases
For tumors that remain difficult to classify, the researchers developed an additional DNA-test that examines changes in chromosome numbers across the entire tumor genome. This method is now used routinely at Amsterdam UMC and, through collaboration with IPATIMUP, also in Portugal.
“This breakthrough gives patients with lung cancer faster and more reliable clarity about their diagnosis. It helps avoid unnecessary treatments and ensures that patients do not miss opportunities for curative therapy. The approach is now considered the international standard for assessing patients with multiple lung tumors” - researcher Bauke Ylstra.
The findings have been published in leading international journals, including the Journal of Thoracic Oncology (2024 en 2025), ESMO Open (2025) and JTO Clinical and Research Reports (2025). An overview article will follow, in which this clinical problem is discussed in depth from the perspective of theories on tumor development.