Post by The Netherlands Cancer Institute

Some DCIS lesions stay quiet. Others carry the genomic signs of something more dangerous. Can we tell the difference earlier? That question is at the heart of new research from the international PRECISION consortium Cancer Grand Challenges, published in Nature Communications Nature Portfolio. Ductal carcinoma in situ (DCIS) is often treated as an early form of breast cancer, yet most DCIS lesions do not progress to invasive disease. Current pathology cannot reliably distinguish indolent lesions from those with true malignant potential, making DCIS one of the most difficult breast cancer diagnoses to manage. Using high-depth whole-genome sequencing, researchers mapped early genomic changes in DCIS lesions to better understand why some may evolve toward invasive breast cancer while others do not. The study was made possible by an international collaboration across the Netherlands, the United Kingdom, and the United States, with major contributions from the Netherlands Cancer Institute and Serena Nik-Zainal at the University of Cambridge. “Using a highly innovative method combining microdissection and whole-genome sequencing, we studied very small DCIS lesions in depth to decipher their genomic landscape in great detail,” says Esther Lips, PhD. One of the key discoveries is SHOREs: Sites of Hotspot Rearrangements and Evolution. These are genomic regions that appear prone to structural rearrangements, potentially caused by transcription-replication conflicts, when DNA reading and copying processes collide. The researchers also found that nearly half of the DCIS lesions showed molecular features linked to more aggressive evolution, including extrachromosomal DNA, or ecDNA. Strikingly, some lesions classified as intermediate-grade under the microscope already carried high-risk genomic features. In other words: what looks moderate under the microscope may tell a much more complex story in the genome. “We show for the very first time at this level that DCIS can exhibit highly complex genomic changes even before invasion occurs,” says Esther Lips. 🔗 https://lnkd.in/ecjUS7cV Research at the NKI is financially supported by KWF Dutch Cancer Society (KWF Kankerbestrijding) and the AVL Foundation. #NKI #DCIS #CancerReseacrh #BreastCancer #PrecisionOncology